Adverse Histopathologic Features Research Articles

Dermoscopy as a Tool for Identifying Potentially Metastatic Thin Melanoma: A Clinical-Dermoscopic and Histopathological Case-Control Study.

Despite being early-stage tumors, thin cutaneous melanomas contribute significantly to mortality and have a rising incidence. A retrospective case-control study was performed to identify clinical-dermoscopic and histopathological variables linked to local and distant metastases in melanomas ≤0.8 mm. Data from 1 January 2000 to 22 June 2022 were analyzed from two Italian skin cancer referral centers. Sixteen patients with ≤0.8 mm melanomas developing metastases were studied compared to controls without metastases over 5 years. Statistical analysis involved Pearson's chi-squared test or Fisher's exact test. Of the 1396 cases, 1.1% progressed. The median diagnosis age was 49 (range 28-83), with 56.3% men and 43.7% women. The torso was the primary tumor site (43.7%). Clinically, lesions were pigmented (>10 mm diameter: 73.3%, ≥3 colors: 80%). Dermoscopically, the common features were white patches (73.3%), atypical vascular patterns (66.5%), blue-gray areas (60%) and absent pigment networks (60%). Histopathologically, all cases had adverse features like regression (87.4%), dermal mitoses (50%), a vertical growth phase (62.5%) and ulceration (12.5%). These findings were statistically significant compared to controls (p < 0.05). In ≤0.8 mm melanomas, specific clinical-dermoscopic traits might indicate higher metastatic potential when paired with adverse histopathological features.

Abstract 2509: Abundant glucocorticoid receptor (GR) expression in human tumors: A tissue microarray study on more more than 18,000 tumors

Abstract The glucocorticoid receptor (GR, or GCR) is a nuclear receptor protein for cortisol and other glucocorticoids and regulates the transcription of thousands of genes involved in metabolism, development, stress, and inflammatory response. In cancer, both an oncogenic and a tumor suppressive function of GR has been proposed. To comprehensively evaluate GR expression in normal and tumorous tissues, a tissue microarray containing 18,570 samples from 147 different tumor types and subtypes and 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC). GR positivity was found in 76.3% of 14,349 interpretable cancers, including 18.5% with weak, 19.6% with moderate, and 38.3% with strong positivity. GR positivity of at least a fraction of tumors was found in all 147 analyzed tumor types and at least one strongly GR positive tumor was found in 136 tumor types. 77 of our 147 tumor entities showed GR positivity of variable intensity in all analyzed cases. 43 further tumor entities showed GR positivity in 80-99.9% of cases. 21 tumor entities had a GR positivity rate between 50 and 80%, including urothelial carcinoma as well as gastric and esophageal adenocarcinoma. Only 6 tumor types had less than 50% GR positive. These included adenomas (21.7-32.5%), adenocarcinomas (17%) and neuroendocrine carcinomas (45.5%) of the colorectum. Reduced GR staining was significantly associated with adverse histopathological and clinical features in several tumor types. Low GR expression was linked to grade progression in pTa (p&amp;lt;0.0001) and to nodal metastasis in pT2-4 urothelial carcinoma of the urinary bladder (p=0.0051), advanced pT stage (p=0.0006) and estrogen receptor positivity (p=0.0126) in breast carcinomas of no special type (NST), as well as to high grade (p≤0.0076), advanced pT stage (p&amp;lt;0.0001), distant metastasis (p=0.0081), and poor overall survival (p=0.002) in clear cell renal cell carcinoma. GR expression was unrelated to clinic-pathological parameters in gastric, pancreatic, and colorectal adenocarcinoma as well as in serous high-grade carcinoma of the ovary. In summary, our data demonstrate frequent GR expression across all cancer types. Significant associations between reduced GR expression and unfavorable tumor features in some but not all tumor types suggest that the functional importance of GR regulated genes for cancer progression depends on the cell of tumor origin. Citation Format: Christina Tsourlakis, Frederike Wegener, Katharina Möller, Martina Kluth, Claudia Hube-Magg, Christian Bernreuther, Guido Sauter, Andreas H. Marx, Ronald Simon, Till Krech, Christoph Fraune, Natalia Gorbokon, Maximilian Lennartz, Sarah Minner, Florian Viehweger. Abundant glucocorticoid receptor (GR) expression in human tumors: A tissue microarray study on more more than 18,000 tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2509.

Contrasting clinical outcomes and socio-economic impact of young versus elderly-onset oral squamous cell carcinoma, a novel health economic analysis.

The incidence of young-onset oral squamous cell carcinoma (OSCC) is growing, even among non-smokers/drinkers. The effects of adverse histopathological features on long-term oncologic outcomes between the young and old are controversial and confounded by significant heterogeneity. Few studies have evaluated the socio-economic impact of premature mortality from OSCC. Our study seeks to quantify these differences and their economic impact on society. Four hundred and seventy-eight young (<45 years) and 1660 old patients (≥45 years) with OSCC were studied. Logistic regression determined predictors of recurrence and death. Survival analysis was calculated via the Kaplan-Meier method. A separate health economic analysis was conducted for India and Singapore. Years of Potential Productive Life Lost (YPPLL) were estimated with the Human Capital Approach, and premature mortality cost was derived using population-level data. Adverse histopathological features were seen more frequently in young OSCC: PNI (42.9% vs. 35%, p = 0.002), LVI (22.4% vs. 17.3%, p = 0.013) and ENE (36% vs. 24.5%, p < 0.001). Although 5-year OS/DSS were similar, the young cohort had received more intensive adjuvant therapy (CCRT 26.9% vs. 16.6%, p < 0.001). Among Singaporean males, the premature mortality cost per death was US $396,528, and per YPPLL was US $45,486. This was US $397,402 and US $38,458 for females. Among Indian males, the premature mortality cost per death was US $30,641, and per YPPLL was US $595. This was US $ 21,038 and US $305 for females. Young-onset OSCC is an aggressive disease, mitigated by the ability to receive intensive adjuvant treatment. From our loss of productivity analysis, the socio-economic costs from premature mortality are substantial. Early cancer screening and educational outreach campaigns should be tailored to this cohort. Alongside, more funding should be diverted to genetic research, developing novel biomarkers and improving the efficacy of adjuvant treatment in OSCC.

Peeping Beyond TNM Stage: Prognostic Factors Affecting Oncological Outcomes in Surgically Treated Early Oral Cancer.

Surgery is the primary modality for the treatment of early oral cancer. The present study aims to evaluate the oncological outcomes, patterns of failure, and prognostic predictors of recurrence in patients of early oral cancer (Stage I and II) treated by surgery alone. It is a single institutional, observational retrospective cohort study conducted from 2012 to 2017.The study was approved by institutional ethics committee. All consecutive patients who underwent upfront curative surgery alone (wide excision of tumour + neck dissection) for pathologically proven early oral cavity SCC(Squamous Cell Carcinoma) pT1-2N0 were included in the study. 113 patients were included in the study after a median follow-up of 58.2months. The median age was 58.5years. 25 patients were stage I, and 88 patients were stage II. The most common subsite was buccal mucosa. There were 31 recurrences and 24 deaths. Using Kaplan Meier method, 3 and 5year overall survival was 92% and 71.8%, respectively, while 3year and 5year recurrence-free survival was 77.9% and 69.4%, respectively. Perineural invasion and poor differentiation affected recurrence-free survival significantly (p value < 0.05). More than one-fourth of surgically treated early oral SCC patients developed recurrence. Presence of poorly differentiated histology and the perineural invasion were the high risk factors which hampered the recurrence free survival. High consumption of betel quid consumption in this part of the world leads to differences in the involved subsite from the Western literature. Adding adjuvant treatment in the presence of these adverse histopathological features may improve prognosis. Randomised studies are warranted to answer this dilemma. Level of Evidence IV.

Short term pathologic outcomes and biochemical recurrence rates of single port transvesical retzius-sparing radical prostatectomy as compared to multiport radical prostatectomy.

369 Background: Single port radical prostatectomy with a transvesical Retzius-sparing approach (SPRP) has shown technical feasibility and early evidence of improved time to urinary continence. How this novel approach leads to differences in pathologic outcomes and biochemical recurrence rates (BCR) as compared to multiport radical prostatectomy (MPRP) has yet to be investigated. Our goal was thus to study the pathologic and short term survival outcomes of patients undergoing SPRP as compared to those undergoing MPRP. Methods: Single center, single surgeon retrospective review of prospectively collected data on 169 patients with low and intermediate risk prostate cancer, whom either underwent SPRP or MRPR (2017-2022). Preoperative clinicopathologic and radiographic characteristics were compared. Following RP, pathologic outcomes, including T stage, grade group (GG), margin status, extraprostatic extension (EPE), seminal vesical invasion (SVI), node retrieval rates, lymph node invasion (LNI) and other adverse histopathologic features were compared between both groups. Cox proportional hazards univariate analysis was used to evaluate the impact of SPRP on biochemical recurrence free survival as compared to MPRP with a three year follow up. Results: A total of 84 patients underwent MPRP and 85 patients underwent SPRP. The SPRP cohort had a higher proportion of clinical T stage one as compared to the MPRP cohort (99% vs 85%, p=0.04), however both groups did not differ preoperatively in terms of median total PSA (6.9 MPRP vs 6.2 SPRP, p=0.24), PI-RADS score (p=0.60) or biopsy GG (p=0.52). Following RP, both groups had similar pathologic outcomes including final grade group, T stage, EPE rates, SVI and Cribriform/intraductal rates (p&gt;0.05). SPRP did yield a lower median number of nodes as compared to MPRP (2 (0-5) vs 6(4-9), p&lt;0.001), but this did not translate to differences in LNI (p=0.08). At a median of approximately 12 months of follow up, there were no differences in the biochemical recurrence-free survival rates among both groups (p=0.38). Cox proportional hazards univariate analysis did not consider SPRP to be an independent predictor of biochemical recurrence (HR 0.53, 95% CI 0.13-2.23, p=0.39). Conclusions: In well selected men, SPRP yields similar short term oncologic control as MPRP with equal rates of margin status, EPE/SVI invasion rates and rates of biochemical recurrence at 1 year. In this small, early, single surgeon experience, SPRP appears to be oncologically safe for low and intermediate risk prostate cancer patients, however longer follow up is necessary, larger numbers and multi- institutional comparisons are needed.

Expression of TP53 in oral squamous cell carcinoma and its correlation with adverse histopathological features

This study aimed to evaluate the expression of TP53 in oral squamous cell carcinoma (OSCC) and to correlate its expressions with adverse histopathological features like depth of invasion (DOI), lymphovascular invasion (LVI), perineural invasion (PNI), extranodal extension (ENE), and margin status which significantly affect the prognosis. This cross-sectional study included 48 patients of OSCC who underwent surgical resection. All the histopathological adverse features such as DOI, LVI, PNI, ENE, margin status were noted. Immunohistochemical expression of TP53 was noted and a correlation of TP53 with histopathological adverse features was done. Statistical analysis was performed using SPSS software. TP53 immunopositivity was seen in 45.83% (22/48) of cases. TP53 has a statistically significant correlation with margin status (P = 0.002). Similarly, TP53 expression is more in cases with LVI (100% cases) though the value is not statistically significant. TP53 expressions are more in positive margin cases and less if the margin is >5 mm. Similarly, TP53 expression is more in cases with LVI (100% cases) though the value is not statistically significant. Few parameters that did not show the correlation of TP53 with adverse histopathological features could be attributed to a small sample size. Further studies with a large number of cases and using other ancillary molecular diagnostic techniques would throw further light on the exact alteration of TP53 in our population and their association with histopathological prognostic features.

The Role of Bone Marrow in Baseline Investigations for Advanced Intraocular Retinoblastoma

Objective: To assess the rationale for bone marrow biopsy/aspiration as a part of a routine systemic workup in advanced intraocular retinoblastoma (RB) in relation to high-risk histopathological post-enucleation features. Methods: A retrospective observational study was conducted at the Department of Pediatric Hematology and Oncology of the Children’s Hospital, Lahore, Pakistan. Data regarding demographics, clinical presentations, staging workup, and treatment strategies of all the newly diagnosed retinoblastoma cases registered at our centre from January 2018 to December 2019 were collected. Statistical analysis was performed using IBM SPSS statistics version 22. Results: Of the 61 patients, 41 (67%) showed unilateral disease, while bilateral and trilateral involvement was found in 17 (28%) and three (5%) cases, respectively. The mean age of presentation in our cohort was 25 months (median: 24 months; range: &lt;1–72 months). Amongst 81 eyes (61 patients), tumours were limited to an intraocular location in 54 eyes (46 patients). In this group, 42 eyes (38 patients) underwent enucleation. Adverse histopathology was found only in nine (23.68%) patients. None of the patients with the intraocular disease, with or without adverse histopathological features in enucleated eyes, were found to have bone marrow (BM) involvement. For 15 patients with extraocular disease, five (33%) patients were found to have bone marrow involvement based on initial investigations. Conclusion: Our study did not show any correlation between bone marrow positivity and advanced intraocular groups D/E RB. Therefore, BM evaluation can be avoided in this subset of patients with retinoblastoma at presentation, while stage III and IV patients (International Retinoblastoma Staging System IRSS) must be evaluated for metastasis. This will reduce the risks of biopsy to the patients and the burden on services. Keywords: Retinoblastoma, Bone Marrow Involvement, Intraocular disease.

Diagnostic and Prognostic Impact of Progesterone Receptor Immunohistochemistry: A Study Evaluating More Than 16,000 Tumors.

Progesterone receptor (PR) is a member of the nuclear/steroid hormone receptor family of ligand-dependent transcription factors. It plays an important role in reproduction and mammary gland development and has various tissue-specific effects in nonreproductive organs. In diagnostic pathology, positive PR immunostaining is used to support a diagnosis of breast or gynecologic origin in a tumor. In this study, the expression of PR was analyzed by immunohistochemistry in 18,176 (interpretable: 16,445) samples from 147 different tumor types and subtypes in a tissue microarray format. PR immunostaining was detected in 57.4% of breast tumors, 28.6% of other gynecological tumors, and 1.8% of nongynecological and nonmammary tumors. Among the group of nongynecological and nonmammary tumors, particularly high rates of PR positivity were seen in neuroendocrine tumors (54.3%) and neuroendocrine carcinomas (35.7%) of the pancreas. A comparison with clinico-pathological parameters showed that reduced PR immunostaining was significantly associated with adverse histopathological and clinical features in breast carcinoma, endometrioid endometrial carcinoma, and pancreatic neuroendocrine tumors. In summary, our analysis of 147 different tumor types for PR immunostaining provides a ranking list of tumor entities according to their prevalence of PR positivity, helps to better understand the diagnostic utility of PR, and highlights the distinct PR positivity among neuroendocrine neoplasms of pancreatic origin.

Elevated IsoPSA Selects for Clinically Significant Prostate Cancer Without a Preference for Any Particular Adverse Histopathologic or Radiographic Feature

OBJECTIVETo explore if elevated IsoPSA selects for particular adverse radiographic or histopathologic features among men destined to undergo radical prostatectomy (RP) because of clinically significant prostate cancer identified at biopsy. MATERIALS AND METHODSSingle center, retrospective review of patients who had undergone IsoPSA testing, prostate biopsy and RP at our institution from 2019-2021. A consecutive cohort of patients whom had undergone RP within the same period without pre-operative IsoPSA served as controls. Pre-operative prostate Magnetic Resonance Imaging (MRI) was included in our analysis. Adverse histopathologic and MRI features were compared between both groups. Concordance, downstaging, and upstaging grade group rates (GG) was evaluated. Pearson Chi-Square test was used to compare categorical variables, Wilcoxon-Rank sum test for quantitative variables, and binary logistic regression to identify predictors of upstaging at RP. RESULTSEighty-three patients underwent IsoPSA and RP while 44 patients were controls. The IsoPSA group had significantly higher pre-operative PSA (IsoPSA group: 7.8 ng/mL vs Control group: 5.2 ng/mL, P<.001 ). Elevated IsoPSA index (>6.0) did not select for any specific adverse histopathologic features at RP. Excluding PSA density, elevated IsoPSA was not selective for adverse MRI features. There were no differences in concordance, downstaging, and upstaging GG rates from biopsy to RP. IsoPSA testing was not a predictor of GG upstaging (Odds Ratio: 0.63, P .58). CONCLUSIONElevated IsoPSA is a diagnostic tool that can detect clinically significant prostate at the time of biopsy. In doing so, it does not select for any particular adverse prostate MRI or pathologic feature at RP.

Prognostic impact of insulin-like growth factor-I and its binding proteins, insulin-like growth factor-I binding protein-2 and -3, on adverse histopathological features and survival outcomes after radical cystectomy.

ObjectivesInsulin‐like growth factor‐I and its binding proteins are involved in cancer development, progression, and metastasis. In urothelial carcinoma, the impact of this pathway is still poorly investigated. The present large cohort study aimed to evaluate the association of preoperative circulating levels of insulin‐like growth factor‐I, insulin‐like growth factor‐I binding protein‐2 and ‐3 on outcomes after radical cystectomy.MethodsA retrospective cohort study of the plasma specimens from 1036 consecutive urothelial carcinoma patients who were treated with radical cystectomy. The primary and secondary outcomes were adverse histopathological features and survival outcomes. Binominal logistic regression and multivariable Cox regression analyses were performed to assess the association of plasma levels of insulin‐like growth factor‐I, insulin‐like growth factor‐I binding protein‐2 and ‐3 with outcomes.ResultsOn multivariable analysis adjusting for the effects of preoperative variables, lower insulin‐like growth factor‐I binding protein‐2 levels were associated with an increased risk of lymph node metastasis and (any non‐organ confined disease) any non‐organ confined disease. Insulin‐like growth factor‐I binding protein‐3 levels were also inversely independently associated with lymph node metastasis. Receiver operating characteristic curve analysis showed that the addition of insulin‐like growth factor‐I binding proteins biomarkers to a reference model significantly improved the discriminating ability for the prediction of lymph node metastasis (+10.0%, P < 0.001). On multivariable Cox regression models, lower levels of both insulin‐like growth factor‐I binding protein‐2 and ‐3 plasma levels were associated with recurrence‐free survival, cancer‐specific survival, and overall survival. insulin‐like growth factor‐I binding protein‐2 and ‐3 levels and improved the discrimination of a standard reference model for the prediction of recurrence‐free survival, cancer‐specific survival, and overall survival (+4.9%, 4.9%, 2.3%, respectively).ConclusionsPreoperative insulin‐like growth factor‐I binding protein‐2 and ‐3 are significantly associated with features of biologically and clinically aggressive urothelial carcinoma. These biomarkers improved prognostic urothelial carcinoma models.

Incorporation of adverse features in advanced oral cancer improves precision in staging and patient prognostication.

Despite revised staging criteria, stratification of patients with advanced oral squamous cell carcinoma (OSCC) remains difficult. Well-established features like perineural invasion (PNI), differentiation, and lymphovascular-invasion (LVI) are controversial, and hence omitted from staging. We endeavor to better stratify this cohort by identifying predictors of survival in advanced OSCC (T3-4). Seven hundred and forty-two patients with T3-4 OSCC underwent surgery from 2006 to 2013. Cox regression was performed to determine predictors of overall survival (OS). OS was adversely impacted by PNI (p=0.046), LVI (p=0.038), moderate/poor differentiation (p=0.001), close/involved surgical margins (p=0.002), pT (p=0.034), and pN (p < 0.001). The cumulative number of adverse histopathological features predicted poorer OS; HR 2.64 (CI 1.42-4.90) for one adverse feature and HR 4.23 (CI 2.34-7.67) for ≥2. In advanced OSCC, stratification with histopathologic risk factors can predict survival even in maximally treated patients; adjuvant therapies are unable to entirely mitigate this risk. Incorporation of adverse features into future editions of TNM can improve precision in staging and identify candidates for treatment escalation.

Abberant Immunohistochemical Expression of OCT3/4 and EMT Related Markers, Vimentin and E-cadherin, is Correlated with Adverse Histopathological Features in Colorectal Adenocarcinoma.

Background: Although clinical management for colorectal cancer has been markedly improved, it is faced with a growing incidence among the young and among those in developing nations. Furthermore, diagnosis occurs mostly in advanced stages, when the therapeutic resources are limited. Therefore we need new biomarkers for diagnostics and therapeutic targets. The key event that leads to invasion and metastasis is the epithelial to mesenchymal transition (EMT), which can be studied with IHC markers. We aimed to corelate the expression of EMT related markers (Vimentin and E-cadherin) and a stem cell marker (OCT 3/4) with the clinicopathological parameters of the tumors. Material and Methods: Surgical resection specimens from 30 treatment-naive colon cancer patients, hospitalized from 2018 to 2021 were assessed. Immunohistochemical tests were performed to investigate the expression of EMT related markers and OCT 3/4 in tumor cells. Results: Vimentin, OCT3/4 positivity and loss of E-cadherin were significantly associated with tumor grade, tumor budding, invasive tumor front, and lymph node metastasis. Conclusions: Vimentin, E-cadherin and OCT 3/4 might serve as a panel of biomarkers that can aid in the prognostication of patients, with the added potential of being oncotargets.

Prevalence of adverse pathology features in grade group 2 prostatectomy specimens with syn- or metachronous metastatic disease.

To validate the importance of recently established adverse histopathology features (cribriform pattern and intraductal carcinoma) as contra-indication for deferred treatment of Gleason score 7 (3 + 4) (grade group [GG] 2) prostate cancer, we investigated their frequency in GG2 radical prostatectomies with syn- or metachronous metastatic disease. GG2 prostatectomy specimens of patients with concomitant lymph node metastasis or distant metastasis at follow-up were identified in a clinical database of a tertiary care center and their pathology was reviewed for pathological stage, lymphovascular invasion, Gleason grade 4 subpatterns, presence of tertiary grade 5, and ductal adenocarcinoma histology. A control group of 99 GG2 prostatectomy specimens who had no metastatic disease (controls) was reviewed for the same adverse pathological features. Of 1860 GG2 prostatectomy specimens (operated between 2002 and 2020), 45 (2.4%) had concurrent regional lymph node metastases or distant metastases at follow-up. Pathological stage distribution of cases and controls was 24% and 79% pT2, 42% and 15% pT3a, 33% and 6.1% pT3b -T4, respectively (p < 0.001). Eleven of 45 cases (24%) had ≤10% Gleason grade 4 component. Cribriform pattern or intraductal carcinoma was present in 84% of cases versus 34% of controls (p < 0.001), tertiary grade 5 in 16% of cases versus 5% controls (p = 0.05) and ductal adenocarcinoma in 16% of cases versus 2% of controls (p = 0.004). Among the seven cases without cribriform or intraductal carcinoma, two displayed ductal adenocarcinoma features. Well-established unfavorable histopathologic features (intraductal and cribriform pattern carcinoma, ductal adenocarcinoma) are represented in about 90% of GG2 prostate cancers with local or distant metastatic disease and are much less common (38%) in those without metastatic disease. Strikingly, about 25% of GG2 prostatectomy cases with metastatic disease had an organ-confined disease and/or a small percentage of Gleason grade 4 pattern. This further emphasizes the relative importance of these adverse histopathological features (cribriform, intraductal, and ductal adenocarcinoma) rather than percentage Gleason grade 4 as contra-indicator of deferred treatment for patients with GG2 prostate cancer.

Risk of Pathologic Extranodal Extension and Other Adverse Features After Transoral Robotic Surgery in Patients With HPV-Positive Oropharynx Cancer

Understanding patient-specific risk of adverse histopathologic findings after primary surgery for human papillomavirus (HPV)-positive oropharynx squamous cell carcinoma (OPSCC) may help guide patient consultations. To determine the likelihood of adverse histopathologic features that may indicate adjuvant radiotherapy or chemoradiotherapy after primary surgery for HPV-positive OPSCC according to 2021 National Comprehensive Cancer Network guidelines. This retrospective cohort study was performed at a single academic tertiary care center. Of 258 patients who underwent transoral robotic surgery (TORS) from March 1, 2012, to March 1, 2021, 136 consecutive, treatment-naive patients with HPV-positive OPSCC without obvious clinical extranodal extension (ENE) who underwent definitive TORS and neck dissection were included in the analysis. Indications for surgical treatment included non-deeply infiltrative oropharynx tumors, minimal soft palate involvement, and low suspicion for pathologic ENE. Primary site TORS with neck dissection. The primary outcomes were the adverse histopathologic features of pathologic ENE and positive surgical margins (PSM) that are indications for possible adjuvant chemoradiotherapy. Outcomes were compared among varying American Joint Committee on Cancer 7th edition (AJCC-7) T and N categories and patient clinical characteristics. Of the 136 patients included in the analysis (113 men [83.1%]; median age, 63 [interquartile range, 55-70] years), 109 (80.1%) had at least 1 indication for possible adjuvant radiotherapy. Twenty-seven patients (19.9%) had pathologic ENE and 10 (7.3%) had PSM. Thirty-four patients (25.0%) had pathologic ENE and/or PSM, whereas 3 (2.2%) had both. Age, smoking history, history of alcohol consumption, and clinical T category were not associated with pathologic ENE, PSM, lymphovascular invasion, perineural invasion, or pN2 category or greater. The proportion of pathologic ENE varied by clinical N category: 0 of 16 for cN0, 8 of 48 (16.7%) for cN1, 3 of 23 (13.0%) for cN2a, and 16 of 45 (35.6%) for cN2b. Compared with patients with cN1-cN2a disease, patients with cN2b disease had higher odds of pathologic ENE (odds ratio, 3.01; 95% CI, 1.14-8.10). Clinical and pathologic N category were concordant in 77 patients (56.6%), whereas 42 (30.9%) were upstaged and 17 (12.5%) were downstaged. In this cohort study, approximately one-quarter of carefully selected patients with HPV-positive OPSCC without obvious clinical ENE undergoing primary surgery had pathologic ENE and/or PSM. Patients with AJCC-7 cT0-cT2 cN0-cN2b disease, especially cN0-cN2a, without signs of clinical ENE may represent appropriate candidates for primary surgery when avoidance of adjuvant chemotherapy and/or reduction of adjuvant radiotherapy dose/extent are the goals.

The Prevalence of Pathogenic or Likely Pathogenic Germline Variants in a Nationwide Cohort of Young Colorectal Cancer Patients Using a Panel of 18 Genes Associated with Colorectal Cancer.

Simple SummaryThis study reveals that pathogenic or likely pathogenic germline variants are detected in one fourth of all young patients with colorectal cancer in a nationwide cohort. Immunohistochemistry staining for mismatch repair deficiency is an easy way to detect Lynch syndrome in the young colorectal cancer patient.Introduction: The prevalence of pathogenic or likely pathogenic germline variants (PGV) in colorectal cancer (CRC) in young patients is seen in approximately one in five patients, with the majority of cases having gene variants associated with Lynch syndrome (LS). The primary aim was to describe the prevalence of 18 genes, all associated with hereditary polyposis and CRC, in a nationwide population of young CRC (yCRC) patients, and outline disease characteristics in patients with or without germline variants. Methods: We screened 98 patients aged 18–40 with CRC diagnosed in 2010–2013 for variants in MSH2, MSH6, MLH1, PMS2, EPCAM, APC, MUTYH, SMAD4, BMPR1A, STK11, PTEN, POLE, POLD1, NTHL1, AXIN2, MSH3, GREM1 and RNF43 using Next Generation Sequencing. Comparisons between patients’ characteristics in patients with PGV, and patients without germline variants (NPGV) were analyzed. Results: PGV were detected in twenty-four patients (24.5%), and twenty-one patients (21.1%) had variants in the mismatch repair (MMR) genes associated with LS. Variants in the APC and MUTYH genes were detected in 1% and 4%, respectively. Patients with NPGV had more advanced disease with adverse histopathological features. Conclusion: PGV was detected in one in four yCRC patients, and one in five yCRC patients had disease causing variants in the mismatch repair genes associated with LS.

Adverse Histopathologic Characteristics in Small Papillary Renal Cell Carcinomas Have Minimal Impact on Prognosis.

Tumor size has long been used in the management decision-making of patients with renal masses. Active surveillance had recently gained traction in selected patients with tumor size of 4 cm or less. Adverse histopathologic characteristics in papillary renal cell carcinoma (PRCC) have been shown to correlate with worse prognosis. We aimed to study whether such features in small PRCCs provide additional prognostic information. Nephrectomies from our institution were collected and reviewed to evaluate for adverse histopathologic features. Clinical follow-up information was collected for all cases. Relationships between the variables were examined by Wilcoxon test and logistic regression. We identified 291 consecutive cases of PRCC. Adverse tumor histopathologic characteristics were significantly related to size. In PRCCs with size greater than 4 cm, there were more cases with high World Health Organization/International Society of Urological Pathology grade and necrosis. Adverse histologic features are less commonly seen in small PRCC and are not associated with lower disease-free survival or disease-specific survival. Identification of these features in small PRCCs (≤4 cm) through needle core biopsy examination would not provide additional prognostic information in patients for whom active surveillance is considered. Clinical and radiologic follow-up in patients with small renal masses that have a known histologic diagnosis of PRCC should be sufficient.

Histopathological features for coexistent invasive cancer in large colorectal adenomatous polyps.

BackgroundHistopathological features associated with coexistent invasive adenocarcinoma in large colorectal adenomas have not been described. This study aimed to determine the association of histopathological features in areas of low-grade dysplasia with coexistent invasive adenocarcinoma.MethodsHigh-grade lesions (containing high-grade dysplasia or adenocarcinoma) from a cohort of large (at least 20 mm) colorectal adenomas removed by endoscopic resection were subjected to detailed histopathological analysis. The histopathological features in low-grade areas with coexistent adenocarcinoma were reviewed and their diagnostic performance was evaluated.ResultsSeventy-four high-grade lesions from 401 endoscopic resections of large adenomas were included. In the low-grade dysplastic areas, a coexistent invasive adenocarcinoma was associated significantly with a cribriform or trabecular growth pattern (P < 0.001), high nuclear grade (P < 0.001), multifocal intraluminal necrosis (P < 0.001), atypical mitotic figures (P = 0.006), infiltrative lesion edges (P < 0.001), a broad fibrous band (P = 0.001), ulceration (P < 0.001), expansile nodules (P < 0.001) and an extensive tumour-infiltrating lymphocyte pattern (P = 0.04). Lesions with coexistent invasive adenocarcinoma harboured at least one of these features. The area under the receiver operating characteristic curve (AUROC) for coexistent invasive adenocarcinoma, using frequencies of adverse histopathological factors in low-grade areas, was 0.92. The presence of two or more of these adverse histopathological features in low-grade areas had a sensitivity of 86 per cent and a specificity of 84 per cent for coexistent invasive adenocarcinoma.ConclusionSeveral histopathological features in low-grade dysplastic areas of adenomas could be predictive of coexistent adenocarcinoma.

Outcomes of patients with metastatic cutaneous squamous cell carcinoma to the axilla: a multicentre cohort study.

Metastatic cutaneous squamous cell carcinoma to the axilla is uncommon, with limited data to guide management. We sought to assess the outcomes of patients with this condition after surgery and radiotherapy. A retrospective cohort study of patients treated at two Australian hospitals from 1994 through 2016 was performed. A total of 74 patients were identified, including 48 treated curatively with surgery-plus-radiotherapy and 15 with surgery alone. Compared with patients treated with surgery alone, a higher proportion of patients treated with surgery-plus-radiotherapy had lymph nodes larger than 6 cm (53% versus 8%, P=0.012) and multiple adverse histopathological features (75% versus 47%, P=0.04). The groups had similar 5-year disease-free survival (45% versus 46%) and overall survival (51% versus 48%). Presence of multiple positive lymph nodes was associated with reduced disease-free survival (hazard ratio 4.57, P=0.01) and overall survival (hazard ratio 3.53, P=0.02). Regional recurrence was higher in patients treated with surgery alone (38% versus 22%, P=0.22) and patients with lymph nodes larger than 6cm (34% versus 10%, P=0.03). All recurrences occurred within 2 years following treatment. Combined-modality therapy for metastatic cutaneous squamous cell carcinoma to the axilla is recommended for high-risk patients, although outcomes remain modest. The key period for recurrence is within 2 years following treatment.

Adenoid cystic carcinoma and basaloid carcinoma of the breast: A clinicopathological study

Adenoid cystic carcinoma of the breast (ACCB) is a rare triple negative tumor (TNT) with an excellent prognosis in most cases. Three different histologic types are recognized: classic ACCB, solid basaloid ACCB (SB-ACCB), and ACCB with high-grade transformation. A majority of these tumors show characteristic molecular and immunohistochemical (IHC) features, with fusion of MYB and NFIB genes and overexpression of MYB, respectively. Basaloid carcinomas of the breast (BCB) are infrequently described. They resemble SB-ACCB and TNT of no special type (TNT-NST).We have studied the clinicopathological features of 17 ACCB and 9 BCB, investigating the expression of MYB by IHC and the rearrangements of MYB by fluorescence in situ hybridization (FISH).MYB was expressed by IHC in 15 ACCB and in 3 BCB. MYB FISH detected rearrangements in 11 ACCB and in 2 BCB.After a mean follow-up of 90 months, with a range of 12–204 months, 2 patients with ACCB with high-grade transformation and 1 patient with BCB developed metastases and died of disease.In summary, most ACCB have a good prognosis, but tumors with adverse histopathological features may metastasize. BCB may overlap with ACCB and TNT-NST, and their prognosis should be further studied.

Poorly differentiated clusters in colorectal cancer: a current review and implications for future practice.

Poorly differentiated clusters (PDC), defined as small groups of ≥5 tumour cells without glandular differentiation, have gained recent attention as a promising prognostic factor in colorectal cancer (CRC). Numerous studies have shown PDC to be significantly associated with other adverse histopathological features and worse clinical outcomes. PDC may hold particular promise in stage II colon cancer, where risk stratification plays a critical role in patient selection for adjuvant chemotherapy. In addition, emerging evidence suggests that PDC can predict lymph node metastasis in endoscopically resected pT1 CRC, potentially helping the selection of patients for oncological resection. In 'head-to-head' comparisons, PDC grade has consistently outperformed conventional histological grading systems both in terms of risk stratification and reproducibility. With a number of large-scale studies now available, this review evaluates the evidence regarding the prognostic significance of PDC, considers its relationship with other emerging invasive front prognostic markers (such as tumour budding and stroma type), assesses its 'practice readiness', addressing issues such as interobserver reproducibility, scoring methodologies and special histological subtypes (e.g. micropapillary and mucinous carcinoma), and draws attention to ongoing challenges and areas in need of further study. Finally, emerging data on the role of PDC in non-colorectal cancers are briefly considered.