Basaloid Subtypes Research Articles

High-risk human papilloma virus status & outcomes for penile squamous cell carcinoma: A single institution experience

ObjectivesThere is a paucity of data on North American cohorts of patients with penile squamous cell carcinoma (pSCC). Herein, we aimed to assess the sensitivity of various modalities to identify human papillomavirus (HPV) status, determine the prevalence of high-risk HPV–positivity, and evaluate the prognostic impact of relevant clinicopathologic variables. MethodsPatients with pSCC (n = 121) consecutively treated with partial/total penectomy (2000–2022) at a single institution were included. HPV status (based on immunohistochemistry [IHC], in situ hybridization [ISH], and panviral metagenomic sequencing [PMS]), histologic features, and outcomes were reviewed. Outcome events included death due to disease and progression. ResultsThe majority of patients were white (105/121, 86.8%). Thirty-seven (30.6%) were high-risk HPV–positive, and morphologic evaluation had a sensitivity of 97.3% (95% confidence interval [CI], 86.2–99.5) for predicting high-risk HPV status compared to IHC/ISH/PMS. Disease progression was more common among high-risk HPV–negative compared to high-risk HPV–positive patients (HR 2.74, CI 1.12–8.23, P = 0.03). Moreover, among high-risk HPV–negative patients, those with moderate-poorly differentiated tumors had increased disease-specific mortality (32.6%, CI 17.1–48.1) compared to those with well-differentiated tumors (0%). Among high-risk HPV–positive patients, those with basaloid morphology had lower disease-specific mortality (0% vs 14.4%, CI 0.0–33.1). ConclusionsWe demonstrate high-risk HPV–positivity in approximately one-third of patients with pSCC. Morphologic evaluation alone had a high sensitivity in correctly determining HPV status. Our results suggest that high-risk HPV status and morphologic features (differentiation in high-risk HPV–negative, and basaloid subtype in high-risk HPV–positive pSCC) may have prognostic value.

Clinical and histopathological factors for recurrence and metastasis in lacrimal gland adenoid cystic carcinoma in Chinese patients.

To investigate the association of metabolism-related proteins and clinicopathological features with poor prognosis in lacrimal gland adenoid cystic carcinoma (LGACC). Clinicopathological data for 39 Chinese patients with LGACC enrolled were retrospectively analysed. Disease progression included death, recurrence, further nodal metastasis, and distant metastasis. Expression of ASCT2 and GLS1 were evaluated by immunohistochemistry. Kaplan-Meier survival curves and Cox proportional hazards regression models were used for risk factor analyses. At the end of follow-up, 14 patients (35.9%) developed local recurrence, 13 patients (33.3%) developed distant metastasis, 3 patients (7.7%) developed lymph node metastasis, and 9 patients (23.1%) died. Among the 13 patients who developed distant metastasis, lung metastasis was observed in 8 patients (61.5%), the brain in 8 patients (61.5%), and bone in 1 patient (7.7%). ASCT2 was expressed in 16 (57.14%) cases, while GLS1 had high expression in 19 (67.9%) cases. Advanced T category (≥T3), bone erosion, basaloid subtype, and ASCT2 (-) were associated with disease progression. Basaloid subtype was an independent risk factor for local recurrence (P = 0.028; HR, 12.12; 95% CI, 1.3-111.5). ASCT2(-) was an independent risk factor for distant metastasis (P = 0.016; HR, 14.46; 95% CI, 1.6-127.5) and was associated with basaloid subtype (P = 0.019). For LGACC, ≥T3 category, basaloid subtype, and bone erosion were high-risk predictors. ASCT2(-) was an independent risk factor for distant metastasis, which suggested that it could be a potential biomarker for LGACC.

Morphological Characteristics of Various Cells in Esophageal Squamous Dysplasia: Extremely Wide Morphological Spectrum.

The WHO classification of esophageal tumors divides esophageal squamous intraepithelial dysplasia into high and low grades, but does not specify its morphological spectrum. Here, the morphological characteristics of various cells were investigated in esophageal squamous (high-grade) dysplasia, and a morphological spectrum and terminology for this lesion were proposed to avoid misdiagnosis. The clinicopathological data of 540 patients with esophageal squamous dysplasia were analyzed retrospectively. According to the unique cytomorphological characteristics of the lesions and the predominant cell type, the esophageal squamous dysplasia was divided into the following morphological groups: classic type (34.6%, 187/540), basaloid subtype (10.7%, 58/540), spindle-cell subtype (4.6%, 25/540), differentiated subtype (48.9%, 264/540), and verrucous subtype (1.1%, 6/540). Gender, age, and lesions location did not differ among the subtypes (P > 0.05), while Paris classification and lesions diameter significantly differed among the subtypes (P < 0.01). Classic-type cells showed severe atypia. In the basaloid subtype, the cells were small, and resembled basal cells; most of these lesions were of the 0-IIb type with small lesion diameter. In the spindle-cell subtype, the cells and nuclei were spindle-shaped or long and spindle-shaped and arranged in parallel. Differentiated-subtype showed well-to-moderately differentiated cells, and epithelial basal cells were mature. Verrucous-subtype showed well-differentiated cells, and were characterized by verrucous or papillary structures. Esophageal squamous dysplasia has extremely wide morphological spectrum. Awareness of the spectrum of morphological presentations of this lesion, specifically the basaloid subtype, spindle-cell subtype, differentiated subtype, and verrucous subtype, is important for accurate diagnosis.

CT findings of basaloid squamous cell carcinoma of the lung in 12 patients: A distinct category of squamous cell carcinoma in 2015 WHO classification of lung tumors.

Basaloid squamous cell carcinoma (SCC) is very rare subtype of SCC of the lung and it is important to distinguish basaloid to other subtypes of SCCs, since the prognosis of basaloid subtype is considered poorer than that of other non-basaloid subtypes of SCCs. Aim of this study was to assess computed tomography (CT) findings of basaloid SCC of the lung in 12 patients.From January 2016 to April 2021, 12 patients with surgically proven basaloid SCC of the lung were identified. CT findings were analyzed, and the imaging features were compared with histopathologic reports. Clinical and demographic features were also analyzed.Axial location of the tumor was central in 5 patients, while 7 was in peripheral. Of the 7 patients whose tumors were located in the peripheral, margin of the tumor were smooth (n = 2), lobulated (n = 2), or spiculated (n = 3). After contrast injection, net enhancement value ranged from 15.8 to 71.8 HU (median, 36.4 HU). Endobronchial growth were seen in 5 patients and these patients accompanied obstructive pneumonia or atelectasis. Internal profuse necrosis, cavitation, or calcifications were not seen.On CT, basaloid squamous cell presents as solitary nodule or mass with moderate enhancement. Tumor was located either peripheral or central compartment of the lung and cavitation was absent.

Epstein-Barr Virus Latent Membrane Protein-1 Expression in Nasopharyngeal Carcinoma.

PURPOSENasopharyngeal carcinoma (NPC), a malignant neoplasm of the epithelium covering the nasopharynx, is a rare disease in most parts of the world. Epstein-Barr virus (EBV), the most potent oncogenic virus, coupled with environmental and genetic factors has been identified to play a role in the development of NPC. An array of methods for detecting the virus do exist, from serologic detection of antibodies to DNA amplification. There is paucity of local data on the status of EBV infection in relation to NPC within the region, and this study attempts to shed more light on the subject.METHODSThis was a retrospective cross-sectional laboratory-based study on histologically confirmed, archived tissues from July 2015 to June 2019. Immunohistochemistry expression of latent membrane protein-1 (LMP-1) was used to detect EBV infection in the tissues.RESULTSA total of 71 cases were enrolled in this study. The mean age was 47.87 years ± 16.84 years with a male-to-female ratio of 1.5:1. There was a unimodal distribution of EBV detection, with the peak (26.8%) at 36-45 years. About 45.1% of the 71 samples tested positive for LMP-1, all of which were nonkeratinizing carcinoma. Nonkeratinizing carcinoma was the most common histopathologic subtype (n = 67; 94.4%), with the majority (38 of 67; 56.7%) being undifferentiated and 29 of 67 (43.3%) differentiated. Keratinizing and basaloid subtypes had two cases each, representing 2.8%.CONCLUSIONA significant proportion of NPC, particularly nonkeratinizing histologic subtype, seems to show LMP-1 positivity by immunohistochemistry, which may be adopted in resource-constrained settings to detect EBV infection in these tissue biopsies.

SMARCB1 (INI1)-deficient sinonasal carcinoma, basaloid subtype: First reported case in Taiwan and literature review

SMARCB1 (INI1)-deficient sinonasal carcinoma is a recently discovered poorly differentiated/undifferentiated sinonasal carcinoma characterized by complete loss of immunoexpression of SMARCB1(INI1) resulting from inactivation of SMARCB1 gene, a known tumor suppressor. Histologically, these tumors have predominant basaloid and rare rhabdoid features. Because other small blue round cell tumors of sinonasal tracts show retained SMARCB1(INI1) expression, this marker should be routinely included in immunohistochemicalpanels together with SMARCA4, p40, p63, p16, NUT, CD99, FLI1, CK7, CD117, and IDH1/2 as well as neuroendocrine markers to make differential diagnoses. If positive for p16, then human papillomavirusin situ hybridization is needed to exclude the possibility of HPV-related tumors. Herein, we describethe first case of SMARCB1 (INI1)-deficient sinonasal carcinoma in Taiwan. The patient, diagnosed as having stage IV disease, was treated with concurrentchemoradiotherapy and remained disease-free at two years, a better outcome than most reported cases. We reviewrelevantliterature to help physicians distinguish this tumor from other ones.

Subtyping salivary gland neoplasm of uncertain malignant potential based on cell type demonstrates differential risk of malignancy.

The newly unveiled Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) has proposed salivary gland neoplasm of uncertain malignant potential (SUMP) as an indeterminate category. The category is reserved for fine-needle aspiration (FNA) cases that are diagnostic of a salivary gland neoplasm but cannot be further designated as a specific tumor type. The objective of the current study was to evaluate the clinical utility of subtyping SUMP cases based on different cell types. A retrospective search of cytology databases at 2 institutions for salivary gland FNAs from 2006 through 2017 was conducted. The cytologic diagnosis of each case was reclassified according to the MSRSGC. Histologic follow-up was retrieved for correlation. Cases reclassified as SUMP that had a follow-up pathologic diagnosis were subject to cytology review and subtyping into oncocytic/squamoid, basaloid, or myoepithelial subtypes based on cytomorphology. The risk of malignancy (ROM) for each subtype was analyzed. There were 92 SUMP cases, which comprised 5.9% of 1560 consecutive salivary gland FNAs within the 12-year study period. Histologic follow-up was available for 59 patients. After cytology review, there were 18 cases (30.5%) of oncocytic/squamoid subtype, 25 (42.4%) of basaloid subtype, and 16 (27.1%) of myoepithelial subtype. Pathologic correlation revealed an ROM of 61.1% (11 of 18 cases) for the oncocytic/squamoid subtype, 40.0% (10 of 25 cases) for the basaloid subtype, and 18.8% (3 of 16 cases) for the myoepithelial subtype. The differences in ROM among the 3 subtypes were statistically significant (P = .0476). Subtyping SUMP cases into categories based on cell type demonstrated differential ROMs for better clinical stratification. Future prospective studies are mandatory to confirm this finding.

Investigation of immune cell markers in feline oral squamous cell carcinoma

Squamous cell carcinoma is the most common oral cancer in the cat and presents as a locally aggressive lesion for which an effective therapeutic protocol remains elusive. Feline oral squamous cell carcinoma (OSCC) shares many clinical characteristics with human head and neck squamous cell carcinoma (HNSCC). Accordingly, present studies were conducted to determine similarities for immune markers shared by feline OSCC and human HNSCC. Biopsies harvested from a feline patient cohort-1 (n = 12) were analyzed for lymphoid cell infiltrates by immunohistochemistry (IHC). Results revealed unique patterns of T cell infiltration involving both neoplastic epithelium and stroma that were detected in most patient tumor biopsies (92%) examined by IHC staining for CD3. Intratumoral B cell infiltrates were detected within tumor stroma only, based on IHC staining for CD79a and CD20 for all patients within the same cohort-1. Infiltration of tumors by a regulatory CD4 T cell subset (Tregs) defined by expression of the forkhead transcription factor FoxP3, was also detected in biopsies from 57% of patients and involved infiltration of neoplastic epithelium and stroma. Patient biopsies were also examined for expression of immunomodulator cyclooxygenase (COX)-2 and revealed positive but weak staining of neoplastic epithelium in a significant proportion of cases (75%). Interestingly, COX-2 expression was detected in both neoplastic epithelium and stroma. Blood collected from a second cohort of feline OSCC patients (n = 9) revealed an increased frequency of circulating CD4+FoxP3+ T cells when compared to healthy adult controls (n = 7) (P = 0.045), although frequencies of CD4+CD25+FoxP3+ T cells were comparable between patients and healthy pet cat controls. Lastly, biopsies from feline OSCC patients were characterized for histologic subtype using a classification scheme previously described for human HNSCC. This analysis revealed the conventional subtype as the predominant variant (75%) with conventional subtypes split evenly between well differentiated and moderately differentiated carcinomas. Two cases were classified as papillary and one case as basaloid subtypes. Correlations between subtype, immune marker scores or circulating Treg frequencies and clinical characteristics or outcome were not detected, most likely due to small patient numbers within patient cohorts. However, findings from these studies provide a preliminary step in the characterization of immune and histologic markers that will be critical to defining prognostic immune markers for feline OSCC and potential targets for testing of immunotherapeutics also relevant to human HNSCC in future studies.

MP37-11 CAN SQUAMOUS CELL CARCINOMA OF THE ANTERIOR MALE URETHRA BE MANAGED BY FOLLOWING A PENILE CANCER BEST PRACTICE PATHWAY?

You have accessJournal of UrologySexual Function/Dysfunction: Penis/Testis/Urethra: Benign Disease & Malignant Disease I1 Apr 2018MP37-11 CAN SQUAMOUS CELL CARCINOMA OF THE ANTERIOR MALE URETHRA BE MANAGED BY FOLLOWING A PENILE CANCER BEST PRACTICE PATHWAY? Aditya Manjunath, Hussain AlNajjar, Catherine Corbishley, Benjamin Ayres, and Nick Watkin Aditya ManjunathAditya Manjunath More articles by this author , Hussain AlNajjarHussain AlNajjar More articles by this author , Catherine CorbishleyCatherine Corbishley More articles by this author , Benjamin AyresBenjamin Ayres More articles by this author , and Nick WatkinNick Watkin More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1217AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Primary squamous cell carcinoma of the anterior male urethra (SCCmu) is rare and the largest published series to date is only 18 patients. In our experience, we believe that SCCmu behaves in a similar way to primary squamous cell carcinoma of the penis (SCCp). In our tertiary referral centre we have managed patients with SCCmu based on our penile cancer pathway in a multi-disciplinary setting in the absence of alternative clinical evidence. We report a comparative study to test the hypothesis that it is oncologically acceptable to manage SCCmu according to the more established SCCp pathway. METHODS Data was collected prospectively on all patients with SCCmu and SCCp from 2001 to 2016. Cases of urothelial tumour, melanoma of urethral origin and metastases to the penis from other sites were excluded. All patients were discussed at our supra-regional MDT and managed according to network guidelines. Management included penile and urethral preserving surgery where possible and inguinal dynamic sentinel node biopsy for cN0 patients (from 2003). Pathology was reported and reviewed by specialist genito-urethral pathologists according to national guidelines. Comparative outcome measures included T stage, grade, histological sub-type and incidence of node positivity in cN0 and cN+ at presentation. 3 year cancer specific survival was calculated with Kaplan-Meier analysis for the 2 groups. RESULTS 77 SCCmu patients and 882 SCCp were compared. T stage (>pT1) 48% SCCmu vs 35% SCCp. High grade disease 78% SCCmu vs 48% SCCp. Basaloid subtypes SCCmu 58% vs 18.3% SCCp. Node negative (pN0) 49% SCCmu vs 60% SCCp. Extra capsular spread (ECS) 26% SCCmu vs 13.3% SCCp. Sentinel node biopsy positivity rate in cN0 28.8% SCCmu vs 22.3% SCCp. 3 year disease specific survival (DSS) 80.5% SCCmu vs 83.6% SCCp. 3 year DSS in the ECS group 55.9% (95% confidence interval 65.8 - 89.3) SCCmu vs 33.7% (95% confidence interval 9.9 - 57.5) SCCp. CONCLUSIONS SCCmu presents with more advanced disease and worse biological characteristics. Nodal drainage is primarily to inguinal nodes. Although 3 year DSS is similar, in the highest risk nodal group 3 year DSS is better in SCCmu with the same treatment algorithm. Our data supports continuing to manage SCCmu patients with our established SCCp pathway. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e495-e496 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Aditya Manjunath More articles by this author Hussain AlNajjar More articles by this author Catherine Corbishley More articles by this author Benjamin Ayres More articles by this author Nick Watkin More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MTE11.01 The Clinical Impact of the 2015 WHO Classification of Lung Tumors

MTE11.01 The Clinical Impact of the 2015 WHO Classification of Lung Tumors

The WHO 2015 classification of lung tumours: Evolution of tumour classification in lung cancer

There are many important changes in the 2015 WHO classification of lung tumours, reflecting the numerous advances in tumour genetics and therapy over the past decade.1 A classification system for small biopsies and cytology is provided for the first time, with emphasis on integration of molecular testing and usage of a limited panel of immunohistochemistry when needed. Adenocarcinoma classification has changed significantly with definitions for adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), and discontinuation of the term bronchioloalveolar carcinoma. Invasive adenocarcinomas are classified according to the predominant pattern, shown to have prognostic significance and also to predict response to adjuvant chemotherapy. These changes will also likely impact on the next TNM staging system in terms of multiple primary tumours and measurement of tumour invasive size. Large cell carcinoma is now restricted to resected tumours that lack clear morphological and immunohistochemical differentiation, with reclassification of those that do to solid adenocarcinoma and non-keratinising squamous cell carcinoma. Squamous cell carcinoma classification is simplified to keratinising, non-keratinising and basaloid subtypes, with the non-keratinising tumours ideally requiring immunohistochemical confirmation. Criteria for diagnosing neuroendocrine tumours remain essentially unchanged but these tumours are now grouped in one category. There are many important changes in the 2015 WHO classification of lung tumours, reflecting the numerous advances in tumour genetics and therapy over the past decade.1 A classification system for small biopsies and cytology is provided for the first time, with emphasis on integration of molecular testing and usage of a limited panel of immunohistochemistry when needed. Adenocarcinoma classification has changed significantly with definitions for adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), and discontinuation of the term bronchioloalveolar carcinoma. Invasive adenocarcinomas are classified according to the predominant pattern, shown to have prognostic significance and also to predict response to adjuvant chemotherapy. These changes will also likely impact on the next TNM staging system in terms of multiple primary tumours and measurement of tumour invasive size. Large cell carcinoma is now restricted to resected tumours that lack clear morphological and immunohistochemical differentiation, with reclassification of those that do to solid adenocarcinoma and non-keratinising squamous cell carcinoma. Squamous cell carcinoma classification is simplified to keratinising, non-keratinising and basaloid subtypes, with the non-keratinising tumours ideally requiring immunohistochemical confirmation. Criteria for diagnosing neuroendocrine tumours remain essentially unchanged but these tumours are now grouped in one category.

The role of histologic subtype, p16(INK4a) expression, and presence of human papillomavirus DNA in penile squamous cell carcinoma.

BackgroundUp to 50% of penile squamous cell carcinomas (pSCC) develop in the context of high-risk human papillomavirus (HR-HPV) infection. Most of these tumours have been reported to show basaloid differentiation and overexpression of tumour suppressor protein p16INK4a. Whether HPV-triggered carcinogenesis in pSCC has an impact on tumour aggressiveness, however, is still subject to research.MethodsIn tissue specimens from 58 patients with surgically treated pSCC between 1995 and 2012, we performed p16INK4a immunohistochemistry and DNA extraction followed by HPV subtyping using a PCR-based approach. The results were correlated with histopathological and clinical parameters.Results90.4% of tumours were of conventional (keratinizing) subtype. HR-HPV DNA was detected in 29.3%, and a variety of p16INK4a staining patterns was observed in 58.6% of samples regardless of histologic subtype. Sensitivity of basaloid subtype to predict HR-HPV positivity was poor (11.8%). In contrast, sensitivity and specificity of p16INK4a staining to predict presence of HR-HPV DNA was 100% and 57%, respectively. By focussing on those samples with intense nuclear staining pattern for p16INK4a, specificity could be improved to 83%. Both expression of p16INK4a and presence of HR-HPV DNA, but not histologic grade, were inversely associated with pSCC tumour invasion (p = 0.01, p = 0.03, and p = 0.71). However, none of these correlated with nodal involvement or distant metastasis. In contrast to pathological tumour stage, the HR-HPV status, histologic grade, and p16INK4a positivity failed to predict cancer-specific survival.ConclusionsOur results confirm intense nuclear positivity for p16INK4a, rather than histologic subtype, as a good predictor for presence of HR-HPV DNA in pSCC. HR-HPV / p16INK4a positivity, independent of histological tumour grade, indicates a less aggressive local behaviour; however, its value as an independent prognostic indicator remains to be determined. Since local invasion can be judged without p16INK4a/HPV-detection on microscopic evaluation, our study argues against routine testing in the setting of pSCC.

Penile intraepithelial neoplasia with pagetoid features: report of an unusual variant mimicking Paget disease

Precancerous lesions of the penis frequently share the morphologic features of the invasive counterpart. We have recently subclassified penile intraepithelial neoplasia into differentiated, warty, and basaloid subtypes, each one with distinctive microscopic morphology. Nevertheless, in our experience, some cases depart from this classification scheme and show unusual morphologic features, hindering the proper diagnosis on routine morphology alone. Herein we present a case of penile intraepithelial neoplasia with a pagetoid growth pattern, closely mimicking Paget disease. We describe the necessary steps to reach the final diagnose, including the use of immunohistochemistry for cytokeratin (CK) 7, CK20, CK34βE12, CAM 5.2, AE1/AE3, CEA, S100, Melan-A, and p63. We also discuss other differential diagnoses that should be considered such as malignant melanoma and urothelial carcinoma in situ with pagetoid spread and less common lesions such as pagetoid dyskeratosis, clear cell papulosis, and mucinous metaplasia.

Basaloid Squamous Cell Carcinoma of the Rectum: A Rare Entity

We report a case of a 33-year old woman with a squamous-cell carcinoma of the rectum, of the basaloid subtype, infiltrating the uterus. The pathologic data and imaging findings that document the presence of the primary tumor of the rectum are presented in detail. Basaloid tumor is a histologic subtype of squamous-cell carcinoma arising usually in the anal canal. In this article we present a case of basaloid carcinoma of the rectum outside the anal canal with a bibliographical review of this rare clinical entity. J Med Cases. 2013;4(8):535-539 doi: http://dx.doi.org/10.4021/ jmc1386e

The prognostic value of tumor-stroma proportion in laryngeal squamous cell carcinoma

Tumor-stroma proportion of tumor has been presented as a prognostic factor in some types of adenocarcinomas, but there is no information about squamous cell carcinomas and laryngeal carcinomas. Five digital images of the tumor sections were obtained from 85 laryngeal carcinomas. Proportion of epithelial tumor component and stroma were measured by a software tool, allowing the pathologists to mark 205.6 μm2 blocks on areas as carcinomatous/stromal, by clicking at the image. Totally, 3.451 mm2 tumor areas have been marked to 16.785 small square blocks for each case. Median follow up was 48 months (range 3-194). The mean tumor-stroma proportion was 48.63+18.18. There was no difference for tumor-stroma proportion when tumor location, grade, stage and perinodal invasion were considered. Although the following results were statistically insignificant, the mean tumor-stroma proportion was the lowest (37.46±12.49) for subglottic carcinomas, and it was 52.41±37.47, 50.86+19.84 and 44.56±16.91 for supraglottic, transglottic and glottic cases. The tumor-stroma proportion was lowest in cases with perinodal invasion and the highest in cases without lymph node metastasis (44.72±20.23, 47.77±17.37, 50.05±17.34). Tumor-stroma proportion was higher in the basaloid subtype compared with the classical squamous cell carcinoma (53.76±14.70 and 48.63±18.38 respectively). The overall and disease-free survival analysis did not reveal significance for tumor-stroma proportion (p=0.08, p=0.38). Only pathological stage was an independent factor for overall survival (p=0.008). This is the first series investigating tumor-stroma proportion as a prognostic marker in laryngeal carcinomas proposing a new method, but the findings do not support tumor-stroma proportion as a prognostic marker.

Basaloid Squamous Cell Carcinoma of the Rectum: A Rare Entity

We report a case of a 33-year old woman with a squamous-cell carcinoma of the rectum, of the basaloid subtype, infiltrating the uterus. The pathologic data and imaging findings that document the presence of the primary tumor of the rectum are presented in detail. Basaloid tumor is a histologic subtype of squamous-cell carcinoma arising usually in the anal canal. In this article we present a case of basaloid carcinoma of the rectum outside the anal canal with a bibliographical review of this rare clinical entity. J Med Cases. 2013;4(8):535-539 doi: http://dx.doi.org/10.4021/ jmc1386e

PD03-04: SuperPathway Analyses of Luminal and Basaloid Breast Cancers from the Cancer Genome Atlas (TCGA) Program.

Abstract The biological and clinical heterogeneity of breast cancer is clearly evident by its different intrinsic transcriptome subtypes. With exception of the HER2 subtype, pathways and signaling networks driving and distinguishing the other major breast cancer subtypes (basaloid, luminal-A, luminal-B) remain largely undefined. As of April 2011, &amp;gt;300 TCGA breast cancer samples have been characterized by both genomic copy number analysis and mRNA expression profiling (44% luminal-A, 26% luminal-B, 16% basaloid). As well, overall survival (OS) data are presently available on 104 luminal-A and 52 luminal-B cases, showing significantly poorer outcome for the latter of these hormonally driven subtypes (log rank p&amp;lt;0.05). Since the poorer outcome of luminal-B breast cancers may be due to their harboring more TP53 gene mutations (∼34%), we used a gene expression signature reported for TP53 mutated estrogen receptor-positive (ER+) breast cancers (Coutant et al., 2011), and confirmed that the TCGA luminal-B cases significantly overexpress this signature relative to luminal-A breast cases in which TP53 mutations are uncommon (6%). Curiously, within each luminal subtype, while this signature correlated with TP53 mutations it did not correlate with TP53 loss of heterozygosity (LOH), which was also higher in luminal-B (∼30%) relative to luminal-A (∼10%) cases. We used the network analysis tool PARADIGM (Vaske et al., Bioinformatics 26, i247-245) to integrate both DNA copy number and transcriptome data and infer pathway activity and interaction differences between luminal-A and luminal-B cases, and between the luminal and basaloid subtypes. This tool merges features derived from curated signal transduction, transcriptional and metabolic pathways into a Superimposed Pathway (SuperPathway) containing ∼3.1K unique activities, 1820 of which revealed significant differences among the breast cancer subtypes (Kruskal-Wallis test, Benjamin Hochberg FDR-corrected p &amp;lt;0.05). From the significant pathway activities differentiating basaloid from luminal-A (1399) or luminal-B (1122) subtypes, assessed using two independent approaches (functional enrichment/EASE scores, subnetwork analysis and hub interconnectivity &amp;gt;10 edges), higher FOXA1 (ER signaling) and lower HIF1A/ARNT transcription factor hub activities emerged as shared luminal differences relative to basaloid breast cancers. Of the 433 significant activities differentiating luminal-A from luminal-B subtypes, MYC/MAX, FOXM1, and MYB emerged as more active hubs in luminal-B, with normal TP53 function as a more active hub in luminal-A breast cancers. In sum, these TCGA analyses offer further insights into the signaling pathways differentiating basaloid from luminal breast cancers, and reveal major transcription factor hubs distinguishing the two common hormone dependent subtypes, luminal-A and luminal-B breast cancers. These findings suggest that SuperPathway analyses may inform therapeutic target opportunities and promote clinical development of breast cancer subtype specific treatment regimens. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD03-04.

Distribution and characterization of subtypes of penile intraepithelial neoplasia and their association with invasive carcinomas: a pathological study of 139 lesions in 121 patients

We are presenting the morphological features of 121 cases of atypical penile intraepithelial lesions. The term penile intraepithelial neoplasia (PeIN) was used to encompass all of them, and lesions were classified into 2 major groups, differentiated and undifferentiated. The latter was further divided in warty, basaloid, and warty-basaloid subtypes. Ninety-five cases were associated with invasive squamous cell carcinomas. Differentiated lesions predominated (68%), followed by warty-basaloid (14%), basaloid (11%), and warty (7%) subtypes. Multifocality was found in 15% of the cases. Differentiated lesions were preferentially located in foreskin, whereas warty and/or basaloid subtypes were more prevalent in the glans. The former lesions were preferentially seen in association with keratinizing variants of squamous carcinoma, whereas the latter subtypes were found mostly in conjunction with invasive warty, basaloid, and warty-basaloid carcinomas. Lichen sclerosus was present in 51% of cases of differentiated lesions and absent in warty and/or basaloid subtypes. In summary, PeIN can be classified into 4 distinctive morphological subtypes. The proper pathological characterization of these lesions may provide important clues to the understanding of the pathogenesis and natural history of penile cancer.

The Relationship between Histologic Grade, Ethnicity, EBV, and HPV Status in Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is a cancer commonly found in South East Asians and has been linked to the Epstein-Barr virus (EBV), specifically those with non-keratinizing or undifferentiated histology. The link between EBV and keratinizing or basaloid subtypes is less well established. A small study has suggested a relationship between keratinizing NPC and oncogenic human papilloma virus (HPV). Here, we evaluate the relationship between tumor histology with ethnicity, EBV, p16 and HPV status.

État des lieux sur les carcinomes basaloïdes ORL

Basaloid squamous cell carcinomas (SCC) are a rare variant of SCC of the head and neck. Their histological characteristics have been described by Wain in 1986 and are reported in the 2005 WHO classification. A poorer prognosis of BSCC has been reported. Two recent case-control studies have shown a higher rate of distant metastases (15-40%, mean over 30%). Conversely, BSCC have similar or better locoregional control rates, a relatively good radiosensitivity and locoregional control. The role of chemotherapy in the neoadjuvant, concomitant or adjuvant setting needs to be redefined due to high metastatic failure rates; chest CT or PET CT are recommended at baseline and every 6-month during follow-up. Some subgroups of BSCC (oropharynx in particular) are more likely to be associated with oncogenic human papilloma virus HPV16. The determination of BSCC head and neck subgroups by HPV status is critical for the prognosis. The basaloid sub-type of squamous cell carcinomas owing to its particular behavior, should be taken into account while deciding the optimal therapeutic strategy.