Excision Specimens Research Articles

Hereditary Parathyroid Disease: Sometimes Pathologists Do Not Know What They Are Missing.

Parathyroid gland excision specimens are common and sometimes underestimated cases that many surgical pathologists encounter regularly. In the vast majority of cases, these will be spot diagnoses of sporadic primary parathyroid adenomas or, perhaps, hyperplasias commonly in the setting of renal failure. However, a small but significant number of parathyroid gland excisions may be due to heritable disease. In most cases, hereditary disease is suspected by the referring clinicians. Nevertheless, a subset of these are undetected which is significant, particularly in the setting of the multiple endocrine neoplasia (MEN), and the hyperparathyroidism jaw tumour (HPT-JT) syndromes. There have been recent advances in recognition of the morphological and immunohistochemical characteristics of these tumours and hyperplasias. While hereditary kindreds are over-represented at specialist referral centres, with awareness of the characteristic clinical and morphological features, the general surgical pathologist is frequently able to suggest the possibility of hereditary parathyroid disease. We therefore provide a succinct guide for pathologists to increase the recognition of hereditary parathyroid disease.

Pilot study to differentiate lipoma from atypical lipomatous tumour/well-differentiated liposarcoma using MR radiomics-based texture analysis.

This pilot study aims to determine if tumour heterogeneity assessed using magnetic resonance imaging (MRI) radiomics-based texture analysis (TA) can differentiate between lipoma and atypical lipomatous tumour (ALT)/well-differentiated liposarcoma (WDL). Thirty consecutive ALT/WDLs and 30 lipomas were included in the study, cases diagnosed both histologically and with murine double minute 2 (MDM2) gene amplification by fluorescence in situ hybridisation (FISH) in excision specimens. Multiple patient, MRI and MRTA factors were assessed. Heterogeneity was evaluated using a filtration-histogram technique-based textural analysis on single axial proton density (PD) and coronal T1-W images of the most homogenously fatty component of the lesion. Thirty-three percent of the diagnoses of ALT/WDL vs lipoma were confirmed using FISH MDM2 analysis. ALT/WDLs were statistically different from lipomas in location (site in the body and depth from skin surface) and fat content, with p values of 0.021, 0.001, and 0.021 respectively. Nine of 36 (25%) texture parameters had significant differences between ALT/WDLs and lipomas on axial PD MRTA, with the most significant results at medium and coarse texture scales particularly mean intensity (p= 0.003) at SSF = 6, and kurtosis (p= 0.012) at SSF = 5. A cut-off value of < 304 for coarse-filtered texture on axial PD MRI identified ALT from lipoma with a sensitivity and specificity of 70% (AUC = 0.73, p= 0.003). Texture heterogeneity quantified at fine, medium, and coarse texture scales are significant differentiators of lipoma and ALT/WDL with the difference particularly marked in medium and coarse texture scales for two MR TA parameters: mean and kurtosis.

Clinico-pathological study of soft tissue tumors

Soft tissue tumors (STT) are a diverse group of tumors. The prognosis of soft tissue tumors is unpredictable and aggressive if not diagnosed early. A vast majority of STT are benign, having a very high cure rate following surgical excision. Benign tumors vary widely in appearance and behavior. The sub-classification of these benign tumors is essential for prognosis as well as clinical management of patients. Histopathology is considered gold standard in the diagnosis of benign STT. To study the clinicopathological profile of benign STT in terms of incidence, age, sex, site distribution, gross and histopathological features and their correlation with clinical diagnosis.This descriptive study included 249 patients with benign STT whose excision specimens were analyzed in the Department of Pathology over five years from January 2013 to December 2017.Benign STT constituted 14.7% of all types of neoplasms in the present study. Among STT, benign tumors formed the majority (92.2%). Adipocytic tumors formed the most common histologic group. Benign STT showed a slight male preponderance with peak incidence in the fourth decade. The most common site of occurrence was the trunk followed by head and neck.With this study, we were able to reassess the clinicopathological profile of benign soft tissue STT and their different types with respect to age, sex, and site distribution.

A Protease-Activated Fluorescent Probe Allows Rapid Visualization of Keratinocyte Carcinoma during Excision.

Keratinocyte carcinomas, including basal and squamous cell carcinomas, are the most common human cancers worldwide. While 75% of all keratinocyte carcinoma (4 million annual cases in the United States) are treated with conventional excision, this surgical modality has much lower cure rates than Mohs micrographic surgery, likely due to the bread-loaf histopathologic assessment that visualizes <1% of the tissue margins. A quenched protease-activated fluorescent probe 6qcNIR, which produces a signal only in the protease-rich tumor microenvironment, was topically applied to 90 specimens ex vivo immediately following excision. "Puzzle-fit" analysis was used to correlate the fluorescent images with histology. Probe-dependent fluorescent images correlated with cancer determined by conventional histology. Point-of-care fluorescent detection of skin cancer had a clinically relevant sensitivity of 0.73 and corresponding specificity of 0.88. Importantly, clinicians were effectively trained to read fluorescent images within 15 minutes with reliability and confidence, resulting in sensitivities of 62%-78% and specificities of 92%-97%. Fluorescent imaging using 6qcNIR allows 100% tumor margin assessment by generating en face images that correlate with histology and may be used to overcome the limitations of conventional bread-loaf histology. The utility of 6qcNIR was validated in a busy real-world clinical setting, and clinicians were trained to effectively read fluorescent margins with a short guided instruction, highlighting clinical adaptability. When used in conventional excision, this approach may result in higher cure rates at a lower cost by allowing same-day reexcision when needed, reducing patient anxiety and improving compliance by expediting postsurgical specimen assessment. SIGNIFICANCE: A fluorescent-probe-tumor-visualization platform was developed and validated in human keratinocyte carcinoma excision specimens that may provide simple, rapid, and global assessment of margins during skin cancer excision, allowing same-day reexcision when needed.

Evaluation of glucocorticoid-induced TNF receptor (GITR) expression in breast cancer and across multiple tumor types.

Glucocorticoid-induced TNF receptor (GITR) is an emerging immunotherapy target that is expressed at high levels on regulatory T cells. Agonistic anti-GITR antibodies have anti-tumor activity in cancer mouse models, and recent phase 1 trials have demonstrated their safe pharmacological profile. However, there is limited knowledge on the relationship between GITR expression and the tumor microenvironment. GITR protein expression was assayed by immunohistochemistry on 3992 breast cancer surgical excision specimens assembled into tissue microarrays and scored visually by a pathologist for GITR expression on tumor-infiltrating lymphocytes and on carcinoma cells. GITR expression by the malignant cells was further surveyed in gastrointestinal stromal tumor (N = 713), lung carcinoma (N = 705), pancreatic cancer (N = 486), ovarian cancer (N = 445), bladder cancer (N = 88), prostate cancer (N = 88), testicular cancer (N = 76), melanoma (N = 75), renal cell carcinoma (N = 68), epithelioid sarcoma (N = 53), and neuroendocrine tumors (N = 41). In breast cancer, GITR expression on tumor-infiltrating lymphocytes (12.4%) correlated with other immune response biomarkers (PD-L1+ on tumor cells, and PD-1+, LAG-3+, TIM-3+ lymphocytes; p < 0.001), and T-cell markers (CD8+, FOXP3+; p < 0.001). GITR+ carcinoma cells were observed in 6.0% of breast cancer cases and correlated with worse relapse-free survival (p = 0.015). Among the additional tumor types examined, cancers with GITR+ malignant cells included bladder cancer (5.7%), primary (but not metastatic) melanoma (4.5%), and ovarian cancer (3.2%); no expression was identified among examined sarcomas. To our knowledge, this is the first immunohistochemistry study to report the frequency and pattern of GITR expression in a large breast cancer cohort, or to report membranous GITR expression on malignant cells. The co-infiltration of GITR with other immune biomarkers and T-cell markers supports a potential role for anti-GITR agents in combination immunotherapies. In addition, GITR expression on carcinoma cells could imply the existence of a novel cancer immune evasion strategy worthy of further investigation.

Can radical surgical treatment of the vulva be justified in the absence of a conclusive diagnosis of squamous cell carcinoma on biopsy? A retrospective 10-year cohort study

ObjectivesThe extent of surgical treatment for vulvar lesions is predominantly guided by the histopathologic diagnosis rendered on the pre-operative biopsy. For premalignant lesions, local excisions are performed, whereas for vulvar squamous cell carcinoma (VSCC), more radical procedures are mandatory. However, even in the absence of a conclusive diagnosis of VSCC on biopsy, the surgeon may opt for a radical excision on grounds of strong clinical suspicion, with a view to avoiding repeat surgeries. We studied a retrospective, 10-year cohort of patients who underwent vulvar excisions, in the absence of a conclusive biopsy diagnosis of VSCC. We aimed to identify the factors predictive of VSCC in these patients, and assess their treatment. Study designAll patients who underwent vulvar excision (2005–2016) at Erasmus MC, without a definitive diagnosis of VSCC on the preoperative biopsy were included. Logistic regression analysis was performed to identify the factors predictive of a final diagnosis of VSCC. Surgical treatment was categorized as definitive, incomplete, or over-treatment, based on histopathology of the excision specimen and previous surgical history. ResultsIn 57 % (64/113) of all included patients, the final diagnosis was VSCC. Higher patient age (p = 0.03), and suspicion of VSCC on pre-operative biopsy (p < 0.001) were associated with a final diagnosis of VSCC on univariate analysis. Suspicion of VSCC on biopsy was the only significant predictor (p < 0.001) on multivariable analysis. For patients with a suspicion of VSCC on biopsy, radical treatment was more frequently performed (p < 0.001), which resulted in over-treatment in only 1 case. Where the surgeon had performed a limited excision despite a suspicion of VSCC on biopsy, high patient age, co-morbidities, location of the tumor close to the anus, and history of previous vulvar surgeries were factors which influenced the decision. The treatment administered was definitive for 72 %., i.e. additional surgeries were not required; 25 % received incomplete treatment and needed additional surgeries, and 3% received over-treatment. ConclusionSuspicion of VSCC on biopsy is strongly predictive of a final diagnosis of carcinoma. In our cohort, radical treatment performed on patients with clinical and histopathological suspicion of VSCC resulted in minimal over-treatment, and helped avoid second surgeries.

Diagnosis and Management of Adenocarcinoma in Situ: A Society of Gynecologic Oncology Evidence-Based Review and Recommendations.

This publication represents an extensive literature review with the goal of providing guidelines for the evaluation and management of cervical adenocarcinoma in situ (AIS). The authors drafted the guidelines on behalf of the Society of Gynecologic Oncology, and the guidelines have been reviewed and endorsed by the ASCCP. These guidelines harmonize with the ASCCP Risk-Based Management Consensus Guidelines and provide more specific guidance beyond that provided by the ASCCP guidelines. Examples of updates include recommendations to optimize the diagnostic excisional specimen, AIS management in the setting of positive compared with negative margins on the excisional specimen, surveillance and definitive management after fertility-sparing treatment, and management of AIS in pregnancy. The increasing incidence of AIS, its association with human papillomavirus-18 infection, challenges in diagnosis owing to frequent origin within the endocervical canal, and the possibility of skip lesions all make AIS a unique diagnosis whose management needs to be differentiated from the management of the more prevalent squamous cell dysplasia.

Molecular Profiling of Keratinocyte Skin Tumors Links Staphylococcus aureus Overabundance and Increased Human β-Defensin-2 Expression to Growth Promotion of Squamous Cell Carcinoma

The skin microbiota plays a prominent role in health and disease; however, its contribution to skin tumorigenesis is not well understood. We comparatively assessed the microbial community compositions from excision specimens of the main human non-melanoma skin cancers, actinic keratosis (AK), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Keratinocyte skin tumors are characterized by significantly different microbial community compositions, wherein AK and SCC are more similar to each other than to BCC. Notably, in SCC, which represents the advanced tumor entity and frequently develops from AK, overabundance of Staphylococcus aureus, a known skin pathogen, was noted. Moreover, S. aureus overabundance was significantly associated with increased human β-defensin-2 (hBD-2) expression in SCC. By challenging human SCC cell lines with S. aureus, a specific induction of hBD-2 expression and increased tumor cell growth was seen. Increased proliferation was also induced by directly challenging SCC cells with hBD-2. Together, our data indicate that a changed microbial community composition in SCC, specified by S. aureus overabundance, might promote tumor cell growth via modulation of hBD-2 expression.

Abstract P4-12-07: Single pre-operative radiation therapy (SPORT) trial for low risk breast cancer: A phase 1 study comparing pathological findings in immediate versus delayed surgery

Abstract Introduction: Estrogen receptor (ER)-positive/HER2-negative breast cancers are known to be less immunogenic than triple negative and HER2-positive breast cancers. As increasing levels of tumor-infiltrating lymphocytes (TILs) have been associated with increased rates of pathological complete response (pCR) and improved prognosis, there is interest in exploring ways to render ER-positive/HER2-negative breast cancers more immunogenic. Few studies have analysed the histological response to neoadjuvant radiation therapy (RT) as the only pre-operative treatment modality; in most case series, chemotherapy was concomitantly given, as these studies focused on the treatment of advanced breast cancer. Aims: The objectives of this study are to assess pathological and immunological responses induced by a single dose of pre-operative RT in early breast cancer. Material and methods: women aged 60 years or older diagnosed with invasive breast carcinoma were prospectively identified. Only cT1N0 unifocal tumors that were low to intermediate grade and ER-positive/HER2 negative were eligible. Patients received a single pre-operative radiation dose of 20Gy in a single fraction. Surgery was performed either 24-72 hours after RT (SPORT group) or 11-13 weeks after RT (SPORT -DS [delayed surgery] group). Assessment of pathological response was performed using the Miller-Payne system and Residual Cancer Burden was calculated. Immunohistochemistry for Ki67 was performed on the biopsy and excision specimens. CD8 immunostain was used to evaluate the immune infiltrate. Both groups (SPORT and SPORT-DS) were compared using the independent t-test and Fisher exact test. Results: a total of thirteen patients were included, with an average age of 73 years (range 60-84). All patients received a single 20Gy radiation dose, and surgery was performed either 24-72 hours after RT (SPORT group, n=5) or on average 95 days after RT in the SPORT-DS group (range 75-133 days; n=8). All patients underwent partial mastectomy with sentinel lymph node biopsy. Histologically, all tumors were invasive ductal carcinomas, except for one invasive micropapillary carcinoma and one invasive tubular carcinoma (both in the SPORT group). Tumor bed changes, similar to what is observed in the post-neoadjuvant chemotherapy setting, were identified in all but one patients in the SPORT-DS group (7/8 patients) but was not seen in the SPORT group (0/5 patients, p=0.005). Using the Miller-Payne system, there was no evidence of response in the SPORT cohort (grade 1/5 in all patients), while 6/8 patients in the SPORT-DS cohort had a partial pathological response (grade 3/5 in 2 patients and grade 4/5 in 4 patients, p = 0.02). No pCR were observed. Comparing Ki67 on the biopsy and surgical specimens, an average decrease of 7.5% in the SPORT group and 6.3% in the SPORT-DS group was observed (p=0.8). A significant lymphocytic infiltrate was not present in any case (stromal TILs &amp;lt;10% in all cases). At an average follow-up of 11 months, there have been no recurrences. Conclusion: This is, to our knowledge, the first series comparing histological findings from immediate and delayed surgery after pre-operative single dose RT. We observed a significant decrease in tumor cellularity with delayed surgery, while no change in cellularity occurred with immediate surgery. The lack of lymphocytic infiltrate does not support immune activation as the mechanism of the ablative effect of 20Gy of radiation. Further follow-up will be needed to determine the prognostic significance of the partial pathological response that was observed in the SPORT-DS cohort. Citation Format: Marie-Hélène Ngo, David Tiberi, Peter Vavassis, David Nguyen, Bernard Fortin, Mai-Kim Gervais, Lucas Sideris, Pierre Dubé, Guy Leblanc, Michel-Pierre Dufresne, Marie-Christine Guilbert, Michael Yassa. Single pre-operative radiation therapy (SPORT) trial for low risk breast cancer: A phase 1 study comparing pathological findings in immediate versus delayed surgery [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-07.

Abstract OT1-01-03: Impact of RANKL inhibition on tumor microenvironment of early-stage breast cancer, a pre-surgical trial

Abstract BACKGROUND: Receptor activator of NF-kB (RANK) and its ligand (RANKL) have a well-established role in osteoclast-driven bone remodeling, however RANK/RANKL expression can also be seen on mammary epithelial cells and immune cells (IC). In breast cancer (BC) mouse models, RANKL is a paracrine effector of the mitogenic activity of progesterone and inhibition of RANKL can attenuate development of BC as well as the incidence of metastases. Pre-clinical evidence demonstrates that RANKL exerts effects on IC such as regulatory T cells (Tregs) and tumor associated macrophages (TAMs) within the tumor microenvironment (TME), thereby promoting tumor progression and metastases. Clinical studies also support a deleterious role for these IC subsets specifically in breast cancer, with high density of either Tregs or TAMs associated with increased risk for distant recurrence. Despite this preclinical support for targeting the RANK/RANKL pathway, clinical trials in early stage BC have had discordant results regarding the clinical benefit of denosumab (RANKL antagonist). As such, it is of significant clinical relevance to identify a drug response signature following treatment as this may suggest biomarkers predictive of benefit from adjuvant denosumab. This window-of-opportunity study was designed to evaluate the pharmacodynamic biomarkers of RANKL inhibition, as well as denosumab’s impact on the TME in paired tumor specimens from patients with BC following treatment with denosumab. Defining the immunomodulatory effects of denosumab may additionally provide biologic rationale for synergistic combination with specific immunotherapy agents. TRIAL DESIGN: This study is a single-arm open label Phase 0 (pre-surgical/window of opportunity) trial. Following diagnostic core needle biopsy, patients receive one dose of denosumab 120 mg given subcutaneously prior to surgical resection. ELIGIBILITY CRITERIA: ≥18 years of age with histologically-confirmed invasive BC &amp;gt;1 cm by radiographic or clinical criteria with available tissue from the core biopsy and planned surgery. Patients are ineligible for this study if neoadjuvant therapy is being considered. STUDY OBJECTIVES: The primary objective is to identify pharmacodynamics markers of RANKL inhibition in early BC. Planned analyses include protein and transcriptomic analyses of known targets of RANKL and compare treatment effect in both RANK/RANKL+ and RANK/RANKL- BC. As a secondary objective, the effect of RANKL inhibition on host immune response will be assessed by comparing pre-treatment biopsy specimens and surgical excision specimens from patients treated with denosumab and untreated controls matched for BC subtype and menopausal status. Planned analyses include RANK/RANKL expression on IC subsets, enumeration of tumor infiltrating lymphocytes by H&amp;E, immunophenotype by immunohistochemistry (e.g. cytotoxic T lymphocytes, Tregs, TAMs) and expression of immune related genes (nanoString Pancancer Immune Panel). STATISTICAL METHODS: As RANK/RANKL protein expression is expected in 25-30% of BC, we plan to enroll 35 subjects to ensure at least 10 subjects with RANK/RANKL+ tumors will be included in our study cohort. With 10 subjects with tumors with high RANK/RANKL expression at baseline, a change from baseline of a single gene of &amp;gt;|1.7| standard deviations between subjects with and without RANK/RANKL expression is detectable based on a 2-sided two sample t-test with power of 80% and false discovery rate of 10%. Differential gene expression analysis will be performed comparing denosumab treated patients with RANK/RANKL+ vs. RANK/RANKL- BC, and between treated patients and untreated controls. PRESENT ACCRUAL: 29 of the planned 35 patients have been enrolled to date. Citation Format: Douglas Kanter Marks, Deborah Axelrod, Maryann Kwa, Nancy Tray, Karen Hiotis, Amber Guth, Yelena Novik, James Speyer, Victor Ty, Adriana Heguy, Judith Goldberg, Farbod Darvishian, Sylvia Adams. Impact of RANKL inhibition on tumor microenvironment of early-stage breast cancer, a pre-surgical trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-01-03.

Completion Surgery in Unfavorable Rectal Cancer after Transanal Endoscopic Microsurgery: Does It Achieve Satisfactory Sphincter Preservation, Quality of Total Mesorectal Excision Specimen, and Long-term Oncological Outcomes?

Unfavorable adenocarcinoma after transanal endoscopic microsurgery requires "completion surgery" with total mesorectal excision. The literature on this procedure is very limited. This study aims to assess the percentage of transanal endoscopic microsurgery that will require completion surgery. This is an observational study with prospective data collection and retrospective analysis from patients who were operated on consecutively. The study was conducted at a single academic institution. Patients undergoing transanal endoscopic microsurgery from June 2004 to December 2018 who later required total mesorectal excision were included. All the patients followed the same protocol: preoperative study, indication of transanal endoscopic microsurgery with curative intent, performance of transanal endoscopic microsurgery, and completion surgery indication 3 to 4 weeks after transanal endoscopic microsurgery. Seven hundred seventy-four patients underwent transanal endoscopic microsurgery, 622 with curative intent (group I: adenoma, 517; group II: adenocarcinoma, 105). Completion surgery was indicated in 64 of 622 (10.3%) patients: group I, 40 of 517 (7.7%) and group II, 24 of 105 (22.9%). After applying exclusion criteria, completion surgery was performed in 55 patients (8.8%). Abdominoperineal resection was performed in 23 (45.1%); the initial lesion was within 6 cm of the anal verge in 19 of these 23 (82.6%). The clinical morbidity rate (Clavien Dindo> II) was 3 of 51 (5.9%). Total mesorectal excision was graded as complete in 42 of 49 (85.7%). The circumferential resection margin was tumor-free in 47 of 50 (94%). Median follow-up was 58 months. Local recurrence was recorded in 2 of 51 (3.9%) and systemic recurrence was recorded in 7 of 51 (13.7%); 5-year disease-free survival was 86%. The limitations are defined by the study's observational design and the retrospective analysis. The indication of completion surgery after transanal endoscopic microsurgery is low, but is higher in the indication of adenocarcinoma. Compared with initial total mesorectal excision, completion surgery requires a higher rate of abdominoperineal resection, but has similar postoperative morbidity, total mesorectal excision quality, and oncological results. See Video Abstract at http://links.lww.com/DCR/B423. ANTECEDENTES:El adenocarcinoma con evolución desfavorable luego de una de microcirugía endoscópica transanal (TEM) requiere "cirugía de finalización" con la excisión total del mesorecto. La literatura sobre este procedimiento es muy limitada.OBJETIVO:Evaluar el porcentaje de microcirugía endoscópica transanal que requerió cirugía completa.DISEÑO:Estudio observacional con recolección prospectiva de datos y análisis retrospectivo de pacientes operados consecutivamente.AJUSTES:El estudio se realizó en una sola institución académica.PACIENTES:Aquellos pacientes sometidos a microcirugía endoscópica transanal desde junio de 2004 hasta diciembre de 2018 que luego requirieron excisón toztal del mesorecto.PRINCIPALES MEDIDAS DE RESULTADO:Todos los pacientes siguieron el mismo protocolo: estudio preoperatorio, indicación de microcirugía endoscópica transanal con intención curativa, realización de microcirugía endoscópica transanal e indicación de cirugía complementaria 3-4 semanas después de la microcirugía endoscópica transanal.RESULTADOS:Setecientos setenta y cuatro pacientes fueron sometidos a microcirugía endoscópica transanal, 622 con intención curativa (grupo I, adenoma: 517, grupo II, adenocarcinoma: 105). la cirugía complementaria fué indicada en 64/622 (10.3%), grupo I: 40/517 (7.7%) y grupo II 24/105 (22.9%). Después de aplicar los criterios de exclusión, la cirugía complementaria se realizó en 55 pacientes (8,8%). La resección abdominoperineal fué realizada en 23 (45,1%); en 19 de estos casos 23 (82,6%) la lesión inicial se encontraba dentro los 6 cm del margen anal. La tasa de morbilidad clínica (Clavien-Dindo > II) fue de 3/51 (5,9%). La excisión total del mesorecto se calificó como completa en 42/49 (85,7%). El margen de resección circunferencial se encontraba libre de tumor en 47/50 (94%). La mediana de seguimiento fue de 58 meses. La recurrencia local se registró en 2/51 (3.9%) y la recurrencia sistémica en 7/51 (13.7%); La supervivencia libre de enfermedad a 5 años fue del 86%.LIMITACIONES:Todas definidas por el diseño observacional y el análisis retrospectivo del mismo.CONCLUSIÓN:La indicación de completar la cirugía después de una TEM es baja, pero es más alta cuando la indicación es por adenocarcinoma. En comparación con la excisión total del mesorecto inicial, la cirugía complementaria requiere una tasa más alta de resección abdominoperineal, pero tiene una morbilidad postoperatoria, una calidad de excisión total del mesorecto y resultados oncológicos similares. ConsulteVideo Resumen en http://links.lww.com/DCR/B423. (Traducción-Dr. Xavier Delgadillo).

Virtual multiplex immunohistochemistry: Application on cell block of effusion and aspiration cytology.

With the continuous development of new antibodies, the use of immunohistochemistry (IHC) is becoming more often a requirement. IHC is frequently necessary for establishing cancer diagnosis and making therapeutic decisions. However, cytology specimens such as effusion fluid and fine-needle aspiration are highly variable in cellularity and contain background inflammatory and mesothelial cells. Compared to biopsy or excision specimens, tissue exhaustion and levels of sections not matching are more commonly encountered. We present a method of integrating whole-slide cell block image of multiple antibodies by digital image processing and reconstructing a virtual multiplex IHC image for enhanced interpretation. Historic archived cell block preparations of carcinomas (n = 19) and melanoma (n = 1) and IHC performed with 3,3'-diaminobenzidine chromogen were reviewed. The slides were digitized by a whole-slide image scanner. Using ImageJ and self-developed code, the slides were aligned by image registration, layered, and recolored to reconstruct a virtual multiplex image, simulating a multiplex preparation with multiple chromogens. To quantity the performance of the image registration, the mean distance between the same cell clusters in aligned images were measured. All 20 cases were successfully registered. The mean distance between cell clusters after image registration was 8.40 +/- 5.52 μm. The reconstructed images were able to demonstrate coexpression of membranous, cytoplasmic, and nuclear antibodies. With virtual multiplex IHC, we were able to visualize coexpression of multiple antibodies without the added cost of multiplex IHC. Routine and historic slides, without additional tissue consumption, can be retrieved for image reconstruction. This technique is a low-cost adjunct to diagnosis in cytology for more efficient and accurate assessment of antibody coexpression and histochemical stains.

Less Than 12 Lymph Nodes in The Surgical Specimen after Neo-Adjuvant Chemo-Radiotherapy in Rectal Cancer: Five Years Survival Analysis

Background: The number of lymph nodes retrieved in the surgical specimen carries prognostic information for the staging and oncological outcomes in colorectal cancer. It was hypothesized that the adequate number of lymph nodes retrieved during surgical clearance is a marker of quality assurance. The paucity of lymph node yield in patients undergoing resection after preoperative chemo-radiotherapy (CRT) in rectal cancer was seen which correlated with tumor regression grade. Lower total number of lymph nodes in the total mesorectal excision (TME) specimen after CRT, might be a marker of better tumor response which supported with better long term oncological outcomes in form of disease-free and overall survival.

Direct intraoperative assessment of total mesorectal excision specimens by expert pathologists in patients with very low rectal cancer prevents unnecessary abdominoperineal resections

In patients with low rectal cancer, the intraoperative assessment of sufficient distal resection margins can be challenging. The assessment determines whether reconstruction can be performed or whether permanent colostomy is required. The goal of the present study was to evaluate intraoperative assessment of the total mesorectal excision (TME) specimen during an interruption of the operation. The intraoperative strategy of eight patients with low rectal cancer was evaluated. In all cases, intraoperative pathological assessment of the TME specimen by an expert pathologist together with the surgeon was performed. Assessment of the distance of the tumor to the resection margin was measured macroscopically as well as microscopically. All patients underwent neoadjuvant chemoradiation. The tumor was located at an average 4.8 ± 1.4cm from the anal verge. In all cases, preoperative MRI revealed mrT3 tumors. The intraoperative assessment showed a median distal resection margin of 10mm (2-15mm). In six patients, sufficient margins allowed for reconstruction while in two patients APR was needed. In three patients (37.5%), the pathological assessment changed the operative strategy: In one patient APR could be avoided while two patients required APR instead of the anticipated TME. The intraoperative assessment of the TME specimen by an expert pathologist together with the surgeon is a valuable tool to avoid unnecessary APR or R1 resections. We therefore suggest routine intraoperative pathological assessment in all operations for borderline low rectal cancers.

Digital Mammography Stereotactic Biopsy versus Digital Breast Tomosynthesis-guided Biopsy: Differences in Biopsy Targets, Pathologic Results, and Discordance Rates.

Background Digital breast tomosynthesis (DBT)-guided biopsy is increasingly used in practice. It is important to know expected changes in biopsy targets, pathologic results, and discordance rates. Purpose To compare biopsy target types, pathologic results, and discordance rates for 2 years preceding and 2 years following implementation of DBT-guided biopsy. Materials and Methods All 9-gauge vacuum-assisted core biopsies from a single tertiary breast center that used digital mammography (DM) stereotactic guidance from 2013 to 2015 and DBT-guided biopsy from 2015 to 2017 were retrospectively reviewed. All mammographic examinations were performed with DBT. Patient demographics, biopsy target type, pathologic reports, surgical excision specimens when available, breast density, and imaging follow-up results were recorded. Biopsy targets and discordance rates between radiologic and pathologic examinations were compared between the two biopsy groups. Generalized mixed modeling was used to examine results before and after DBT-guided biopsy. Results A total of 1313 women underwent 1405 breast biopsies: 643 by using DM (August 2013 to July 2015) (median age, 56 years; interquartile range, 49-66 years) and 762 by using DBT (August 2015 to July 2017) (median age, 58 years; interquartile range, 50-67 years), (P = .58). Calcifications were the most common biopsy target for both groups, constituting 89.9% (578 of 643) of DM-guided biopsies and 71.1% (542 of 762) of DBT-guided biopsies (P = .03). The rate of architectural distortion biopsies was 2.0% (13 of 643) with DM-guided biopsy and 17.7% (135 of 762) with DBT-guided biopsy (P = .01). Although overall malignancy rate was similar for DM-guided biopsy (27.8% [179 of 643]) and DBT-guided biopsy (24.8% [191 of 762], P = .54), DBT-guided biopsy helped identify a similar percentage of invasive malignancies (37.4% [72 of 191] vs 29.0% [52 of 179] at DM P = .35), but more radial sclerosing lesions (8.3% [95% confidence interval {CI}: 6.0, 10.0] vs 1.7% [95% CI: 1.0, 3.1]) (P = .01). The discordance rate was 1.4% (95% CI: 1.0, 2.7) with DM-guided biopsy and 4.5% (95% CI: 3.2, 6.3) with DBT-guided biopsy (P = .01). Of the 34 discordant DBT-guided biopsies, 30 were architectural distortions. Conclusion With the transition to digital breast tomosynthesis-guided biopsy, more architectural distortions were biopsied, more radial sclerosing lesions were identified, and more discordance existed in radiologic and pathologic examinations, with a similar percentage of carcinomas diagnosed. © RSNA, 2020 Online supplemental material is available for this article.

Immunohistochemical analysis of IDH2 R172 hotspot mutations in breast papillary neoplasms: applications in the diagnosis of tall cell carcinoma with reverse polarity.

Tall cell carcinoma with reverse polarity is a rare subtype of breast carcinoma with solid and papillary growth and nuclear features reminiscent of those of the tall cell variant of papillary thyroid carcinoma. These tumors harbor recurrent IDH2 R172 hotspot mutations or TET2 mutations, co-occurring with mutations in PI3K pathway genes. Diagnosis of tall cell carcinomas with reverse polarity is challenging in view of its rarity and the range of differential diagnosis. We sought to determine the sensitivity and specificity of IDH2 R172 immunohistochemistry for the detection of IDH2 R172 hotspot mutations in this entity. We evaluated 14 tall cell carcinomas with reverse polarity (ten excision and five core needle biopsy specimens), 13 intraductal papillomas, 16 solid papillary carcinomas and five encapsulated papillary carcinomas by Sanger sequencing of the IDH2 R172 hotspot locus and of exons 9 and 20 of PIK3CA, and by immunohistochemistry using monoclonal antibodies (11C8B1) to the IDH2 R172S mutation. The fourteen tall cell carcinomas with reverse polarity studied harbored IDH2 R172 hotspot mutations, which co-occurred with PIK3CA hotspot mutations in 50% of cases. None of the other papillary neoplasms analyzed displayed IDH2 R172 mutations, however PIK3CA hotspot mutations were detected in 54% of intraductal papillomas, 6% of solid papillary carcinomas and 20% of encapsulated papillary carcinomas tested. Immunohistochemical analysis with anti-IDH2 R172S antibodies (11C8B1) detected IDH2 R172 mutated protein in 93% (14/15) of tall cell carcinomas with reverse polarity samples including excision (n=9/10) and core needle biopsy specimens (n=5), whereas the remaining papillary neoplasms (n=34) were negative. Our findings demonstrate that immunohistochemical analysis of IDH2 R172 is highly sensitive and specific for the detection of IDH2 R172 hotspot mutations, and likely suitable as a diagnostic tool in the evaluation of excision and core needle biopsy material of tall cell carcinomas with reverse polarity.

Analysis of lymphatic drainage pathways using infrared fluorescence in patients with lung cancer

To develop a method for analysis of lymphatic drainage pathways from the lobe of the lung affected by non-small cell lung cancer (NSCLC) using infrared fluorescence. A study enrolled patients with NSCLC who underwent anatomic resection of the lung with systematic lymph node dissection and preliminary intraoperative peritumoral injection of indocyanine green conjugate with human albumin. Registration of fluorescence in regional lymph nodes (LN) was carried out immediately after excision of specimen using the FLUM-808 instrumental system. Infrared fluorescence was observed in 117 hilar and mediastinal lymph nodes from 43 patients (2.7 nodes per a patient). Comparison of localization of fluorescent LN with localization of tumor in various lobes established significant variability of lymphatic drainage pathways. The developed method of infrared fluorescent evaluation of lymphatic drainage in patients with NSCLC confirms the necessity of systematic lymph node dissection for adequate staging.

Case report and review of solitary cutaneous focal mucinosis: a unique primary cutaneous mucinosis unrelated to mucinosis-associated systemic diseases

Localized deposition of mucin in the upper dermis is referred to as cutaneous focal mucinosis. Patients with this condition either present with a single skin lesion (solitary cutaneous focal mucinosis) or numerous skin lesions (multiple cutaneous focal mucinosis). A man with solitary cutaneous focal mucinosis is described and the features of this condition are reviewed. Solitary cutaneous focal mucinosis has a slight male predominance and typically presents in adults, ranging in age from 29 years to 60 years, as a nodule or papule that is flesh-colored or white and most commonly located on an extremity or the trunk. Microscopic examination shows deposition of mucin in the upper dermis; the overlying epidermis can be normal, atrophic or hyperplastic. The skin lesion is often removed at the time of biopsy. However, recurrence has not been observed when the mucin deposition is present at the edge of the biopsy or excision specimen. Although the pathogenesis of this condition remains to be established, in contrast to individuals with multiple cutaneous focal mucinosis, solitary cutaneous focal mucinosis is a unique primary cutaneous mucinosis unrelated to mucinosis-associated systemic diseases.

Splenic flexure mobilization in surgery for rectal cancer

Nowadays, the issue of splenic flexure mobilization (SFM) in anterior and low anterior rectal resection for rectal cancer is still debatable. This stage is important because dissection results tension-free anastomosis and excision of specimen of enough length with adequate number of harvested lymph nodes. However, literature review confirmed the absence of agreement regarding reduced incidence of colorectal anastomotic leakage and improved long-term oncologic outcomes after SFM. Opinion about selective approach to this procedure is becoming more common. Therefore, randomized trials are necessary to determine a need for routine SFM or indications for selective approach to SFM in anterior rectal resection for rectal cancer.

Cell block versus fine-needle aspiration cytology in the diagnosis of breast lesions

Background: Breast cancer is the most common cancer worldwide. Fine-needle aspiration cytology (FNAC) is an outpatient simple procedure, which gives a quick cytological diagnosis for breast lesions. Cell blocks prepared from the aspirated material of these breast lumps not only serve as useful adjunct to FNAC, but also give tissue diagnosis comparable to breast biopsies. Aims and Objectives: This study was undertaken to assess the utility of cell block technique in diagnosing various breast lesions in correlation with FNAC findings. Subsequent histopathology diagnosis was obtained and compared with cytological diagnosis wherever possible. Materials and Methods: A prospective cross-sectional study was done for a period of 2 years. A total of 130 cases of breast lumps were studied with both FNAC and cell block techniques. The cell block findings were then correlated with FNAC diagnosis and statistically analyzed. Histopathology findings of subsequent biopsy or excision specimen of breast lumps were obtained wherever possible. Results: Out of the total 130 cases, most of the cases were benign lesions (58%), with fibroadenoma being the most common (97%). Among malignant tumors, invasive mammary carcinoma of no special type was the most common type (94.7%). Cell blocks were more accurate (88.8%) compared to FNAC (69.2%) in diagnosing both benign and malignant lesions. Conclusion: Cell block method is superior to FNAC in the diagnosis of both benign and malignant tumors of the breast and helps to eliminate the need for invasive breast biopsies