[Construction of a model based on multipoint full-layer puncture biopsy for predicting pathological complete response after neoadjuvant therapy for locally advanced rectal cancer].

Objective: To investigate the value of transanal multipoint full-layer puncture biopsy (TMFP) in predicting pathological complete response (pCR) after neoadjuvant radiotherapy and chemotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) and to establish a predictive model for providing clinical guidance regarding the treatment of LARC. Methods: In this multicenter, prospective, cohort study, we collected data on 110 LARC patients from four hospitals between April 2020 and March 2023: Beijing Chaoyang Hospital of Capital Medical University (50 patients), Beijing Friendship Hospital of Capital Medical University (41 patients), Qilu Hospital of Shandong University (16 patients), and Zhongnan Hospital of Wuhan University (three patients). The patients had all received TMFP after completing standard nCRT. The variables studied included (1) clinicopathological characteristics; (2) clinical complete remission (cCR) and efficacy of TMFP in determining pCR after NCRT in LARC patients; and (3) hospital attended, sex, age, clinical T- and N-stages, distance between the lower margin of the tumor and the anal verge, baseline and post-radiotherapy serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9 concentrations, chemotherapy regimen, use of immunosuppressants with or without radiotherapy, radiation therapy dosage, interval between surgery and radiotherapy, surgical procedure, clinical T/N stage after radiotherapy, cCR, pathological results of TMFP, puncture method (endoscopic or percutaneous), and number and timing of punctures. Single-factor and multifactorial logistic regression analysis were used to determine the factors affecting pCR after NCRT in LARC patients. A prediction model was constructed based on the results of multivariat analysis and the performance of this model evaluated by analyzing subject work characteristics (ROC), calibration, and clinical decision-making (DCA) curves. pCR was defined as complete absence of tumor cells on microscopic examination of the surgical specimens of rectal cancer (including lymph node dissection) after NCRT, that is, ypT0+N0. cCR was defined according to the Chinese Neoadjuvant Rectal Cancer Waiting Watch Database Study Collaborative Group criteria after treatment, which specify an absence of ulceration and nodules on endoscopy; negative rectal palpation; no tumor signals on rectal MRI T2 and DWI sequences; normal serum CEA concentrations, and no evidence of recurrence on pelvic computed tomography/magnetic resonance imaging. Results: Of the 110 patients, 45 (40.9%) achieved pCR after nCRT, which was combined with immune checkpoint inhibitors in 34 (30.9%). cCR was diagnosed before puncture in 38 (34.5%) patients, 43 (39.1%) of the punctures being endoscopic. There were no complications of puncture such as enterocutaneous fistulae, vaginal injury, prostatic injury, or presacral bleeding . Only one (2.3%) patient had a small amount of blood in the stools, which was relieved by anal pressure. cCR had a sensitivity of 57.8% (26/45) for determining pCR, specificity of 81.5% (53/65), accuracy of 71.8% (79/110), positive predictive value 68.4% (26/38), and negative predictive value of 73.6% (53/72). In contrast, the sensitivity of TMFP pathology in determining pCR was 100% (45/45), specificity 66.2% (43/65), accuracy 80.0% (88/110), positive predictive value 67.2% (45/67), and negative predictive value 100.0% (43/43). In this study, the sensitivity of TMFP for pCR (100.0% vs. 57.8%, χ2=24.09, P<0.001) was significantly higher than that for cCR. However, the accuracy of pCR did not differ significantly (80.0% vs. 71.8%, χ2=2.01, P=0.156). Univariate and multivariate logistic regression analyses showed that a ≥4 cm distance between the lower edge of the tumor and the anal verge (OR=7.84, 95%CI: 1.48-41.45, P=0.015), non-cCR (OR=4.81, 95%CI: 1.39-16.69, P=0.013), and pathological diagnosis by TMFP (OR=114.29, the 95%CI: 11.07-1180.28, P<0.001) were risk factors for pCR after NCRT in LARC patients. Additionally, endoscopic puncture (OR=0.02, 95%CI: 0.05-0.77, P=0.020) was a protective factor for pCR after NCRT in LARC patients. The area under the ROC curve of the established prediction model was 0.934 (95%CI: 0.892-0.977), suggesting that the model has good discrimination. The calibration curve was relatively close to the ideal 45° reference line, indicating that the predicted values of the model were in good agreement with the actual values. A decision-making curve showed that the model had a good net clinical benefit. Conclusion: Our predictive model, which incorporates TMFP, has considerable accuracy in predicting pCR after nCRT in patients with locally advanced rectal cancer. This may provide a basis for more precisely selecting individualized therapy.

[Application of optical coherence tomography in the evaluation of cervical lesions: a multicenter study].

Objective: To explore the value of optical coherence tomography (OCT) imaging system in evaluating cervical lesions in vivo. Methods: A total of 1 214 patients with cervical lesions were collected from January 2020 to December 2021 in the Third Affiliated Hospital of Zhengzhou University, Maternal and Chlid Heaith Hospital of Gushi County, Xinyang City, Henan Province, and Maternal and Chlid Heaith Hospital of Sui County, Shangqiu City, Henan Province. The age of the patients was (38.9±10.5) years (range: 16-77 years). All patients underwent in vivo cervical OCT examination and cervical biopsy pathology examination, and summarized the OCT image features of in vivo cervical lesions. Using the pathological diagnosis as the "gold standard", the accuracy, specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of OCT image interpretation results were evaluated, as well as the consistency of OCT image diagnosis and pathological diagnosis. At the same time, the in vivo cervical OCT imaging system, as a newly developed screening tool, was compared with the traditional combined screening of human papillomavirus (HPV) and Thinprep cytologic test (TCT), to assess the screening effect. Results: By comparing the OCT images of the cervix in vivo with the corresponding HE images, the OCT image characteristics of the normal cervix and various types of cervical lesions in vivo were summarized. The accuracy, sensitivity, specificity, PPV and NPV of OCT image in the diagnosis of high-grade squamous intraepithelial lesion (HSIL) and above (HSIL+) were 93.4%, 88.5%, 95.0%, 85.0% and 96.2%, respectively. The accuracy, sensitivity, specificity, PPV and NPV of OCT for low-grade squamous intraepithelial lesion (LSIL) were 84.7%, 61.7%, 96.3%, 89.3% and 83.2%, respectively. The consistency between OCT image diagnosis and pathological diagnosis was strong (Kappa value was 0.701).The accuracy, sensitivity and specificity of OCT screening, HPV and TCT combined screening were 83.7% vs 64.9% (χ²=128.82, P<0.001), 77.8% vs 64.5% (χ²=39.01, P<0.001), 91.8% vs 65.4% (χ²=98.12, P<0.001), respectively. The differences were statistically significant. Conclusions: OCT imaging system has high sensitivity and specificity in the evaluation of cervical lesions in vivo, and has the characteristics of non-invasive, real-time and high efficiency. OCT examination is expected to become an effective method for the diagnosis of cervical lesions and cervical cancer screening.

[Efficacy analysis of 7 cases of mixed neuroendocrine-nonneuroendocrine neoplasm of the duodenal papilla].

The clinical data of 7 patients diagnosed with mixed neuroendocrine-nonneuroendocrine neoplasm were analyzed in the Department of Hepatobiliary Surgery of Hunan Provincial People's Hospital from January 2016 to December 2022. Among the 7 patients, 5 were male and 2 were female, with an average age of 59.3 years. Its clinical characteristics are similar to malignant ampulla tumors, and it is difficult to differentiate them. The preoperative puncture biopsy positivity rate is low, making it difficult to diagnose preoperatively, and the prognosis is worse.Comprehensive treatment including surgery, chemotherapy, and radiotherapy can be the preferred treatment option for this disease.

Recurrent Marginal Zone Lymphoma with Bone Marrow Involvement Detected by ¹8F-FDG PET/CT and Biopsy: A Diagnostic Challenge.

BACKGROUND Marginal zone lymphoma is a low-grade, B-cell, non-Hodgkin lymphoma. Bone marrow involvement (BMI) of leukemia or lymphoma can usually be displayed in fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (¹8F-FDG PET/CT) with high standardized uptake values (SUV), while diffuse homogeneous ¹8F-FDG bone marrow uptake (BMU) in PET/CT primarily reflects hyperplastic bone marrow status. This report is of a 74-year-old man presenting with anemia and a diagnosis of recurrent marginal zone lymphoma with bone marrow involvement identified with 18F-FDG PET/CT imaging and biopsy. CASE REPORT A 64-year-old man with severe anemia and body weight loss of 7 kg in 1 month was diagnosed with marginal zone lymphoma, stage III, in July 2011. He went into complete remission in April 2012 after 6 cycles of chemotherapy, with Hb restored. Anemia and diffuse homogeneous ¹8F-FDG BMU in PET/CT were then noted during a routine check-up in October 2021, and recurrent disease was established through positive biopsy of subcutaneous nodules and bone marrow. Subsequent complete remission after 6 cycles of combination therapy was validated with pathologically negative BMI, the resolution of the slightly enhanced ¹8F-FDG BMU in PET/CT, and restored hemoglobin. CONCLUSIONS This report has highlighted the importance of follow-up for patients with lymphoma and supports the diagnostic role of ¹8F-FDG PET/CT imaging and the pathological verification in identifying malignant involvement in bone marrow.

Cotrimoxazole and targeted antibiotic prophylaxis for transrectal prostate biopsy: a single-center study.

PURPOSE: The recent restriction on the use of fluoroquinolones for prophylaxis by the European Commission has left a gap in clear recommendations for practical antibiotic prophylaxis (PAP) for transrectal prostate biopsy (TRPB). This analysis investigated the viability of cotrimoxazole for PAP in TRPB. METHODS: This analysis included n = 697 patients who underwent TRPB for suspected prostate cancer (PCa). All patients received either empiric PAP with four doses of cotrimoxazole 960 mg or targeted antibiotic prophylaxis in case of a positive rectal or urine screening for multiresistant gram-negatives. Infectious complications after TRPB, microbiological findings, and clinical characteristics were evaluated. A multivariable logistic regression model was calculated to identify variables associated with infectious complications. RESULTS: Of the cohort, 86% (600/697) received PAP with cotrimoxazole, 1% (8/697) received cotrimoxazole plus an additional antibiotic, 4% (28/697) received amoxicillin + clavulanic acid, 4% (28/697) received fluoroquinolones, and 5% (33/697) received a single shot intravenous antibiotic prophylaxis with meropenem or piperacillin + tazobactam due to multiresistant microbiological findings in either pre-interventional urine culture or rectal swab. Infectious complications occurred in 2.6% (18/697) of patients. Fever was noted in 89% (16/18) of cases. Inpatient treatment was given to 67% (12/18) of affected patients, with 38% (7/18) having positive blood cultures, identifying cotrimoxazole-resistant E. coli strains in six out of seven cases. Multivariable logistic regression analysis revealed no clinically significant variables, including PAP with cotrimoxazole, as independent risk factors for an infectious complication. CONCLUSIONS: Using cotrimoxazole as PAP for TRPB in cases without multiresistant gram-negatives in pre-interventional urine cultures or rectal swabs seems feasible and practical.

Development and validation of a novel nomogram model for predicting delayed graft function in deceased donor kidney transplantation based on pre-transplant biopsies.

BACKGROUND: Delayed graft function (DGF) is an important complication after kidney transplantation surgery. The present study aimed to develop and validate a nomogram for preoperative prediction of DGF on the basis of clinical and histological risk factors. METHODS: The prediction model was constructed in a development cohort comprising 492 kidney transplant recipients from May 2018 to December 2019. Data regarding donor and recipient characteristics, pre-transplantation biopsy results, and machine perfusion parameters were collected, and univariate analysis was performed. The least absolute shrinkage and selection operator regression model was used for variable selection. The prediction model was developed by multivariate logistic regression analysis and presented as a nomogram. An external validation cohort comprising 105 transplantation cases from January 2020 to April 2020 was included in the analysis. RESULTS: 266 donors were included in the development cohort, 458 kidneys (93.1%) were preserved by hypothermic machine perfusion (HMP), 96 (19.51%) of 492 recipients developed DGF. Twenty-eight variables measured before transplantation surgery were included in the LASSO regression model. The nomogram consisted of 12 variables from donor characteristics, pre-transplantation biopsy results and machine perfusion parameters. Internal and external validation showed good discrimination and calibration of the nomogram, with Area Under Curve (AUC) 0.83 (95%CI, 0.78-0.88) and 0.87 (95%CI, 0.80-0.94). Decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSION: A DGF predicting nomogram was developed that incorporated donor characteristics, pre-transplantation biopsy results, and machine perfusion parameters. This nomogram can be conveniently used for preoperative individualized prediction of DGF in kidney transplant recipients.

Expected impact of MRI-targeted biopsy interreader variability among uropathologists on ProScreen prostate cancer screening trial: a pre-trial validation study.

PURPOSE: Prostate cancer (PCa) histology, particularly the Gleason score, is an independent prognostic predictor in PCa. Little is known about the inter-reader variability in grading of targeted prostate biopsy based on magnetic resonance imaging (MRI). The aim of this study was to assess inter-reader variability in Gleason grading of MRI-targeted biopsy among uropathologists and its potential impact on a population-based randomized PCa screening trial (ProScreen). METHODS: From June 2014 to May 2018, 100 men with clinically suspected PCa were retrospectively selected. All men underwent prostate MRI and 86 underwent targeted prostate of the prostate. Six pathologists individually reviewed the pathology slides of the prostate biopsies. The five-tier ISUP (The International Society of Urological Pathology) grade grouping (GG) system was used. Fleiss' weighted kappa (κ) and Model-based kappa for associations were computed to estimate the combined agreement between individual pathologists. RESULTS: GG reporting of targeted prostate was highly consistent among the trial pathologists. Inter-reader agreement for cancer (GG1-5) vs. benign was excellent (Model-based kappa 0.90, Fleiss' kappa κ = 0.90) and for clinically significant prostate cancer (csPCa) (GG2-5 vs. GG0 vs. GG1), it was good (Model-based kappa 0.70, Fleiss' kappa κ 0.67). CONCLUSIONS: Inter-reader agreement in grading of MRI-targeted biopsy was good to excellent, while it was fair to moderate for MRI in the same cohort, as previously shown. Importantly, there was wide consensus by pathologists in assigning the contemporary GG on MRI-targeted biopsy suggesting high reproducibility of pathology reporting in the ProScreen trial.

Breast mucosa-associated lymphoid tissue lymphoma: A case report and literature review.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma, also known as extranodal marginal zone lymphoma, is more commonly detected in the stomach and rarely in the breast. Our study presented a clinical and pathological examination of a patient diagnosed with breast MALT lymphoma, supplemented with pertinent research, to offer guidance for the diagnosis and treatment of this condition. PEOPLE CONCERNS: The occurrence of breast MALT lymphoma has risen in the past decade, but its etiology, progression and treatment response are less well-studied. DIAGNOSIS: Breast MALT lymphoma was diagnosed by excisional biopsy and histopathology. INTERVENTIONS: Following breast MALT lymphoma diagnosis, the patient was transferred to the hematology department for further treatment, and she made the decision to continue observing. OUTCOMES: After 3 months of observation, the patient remained asymptomatic. CONCLUSION: Breast MALT lymphoma is an indolent disease with an asymptomatic presentation, There are no standardized treatment guidelines for breast MALT lymphoma, treatment must be tailored to the patient willingness to treat and the severity of the disease. Hence, in order to give patients a better chance of cure, more research is needed to explore its pathogenesis and more clinical trials are needed investigate the treatment of this disease.

History of chronic gastritis: How our perceptions have changed.

Currently, the diagnostic strategy for chronic gastritis (CG) is aimed not just at fixing the presence of gastric mucosal inflammation, but also at gastric cancer (GC) risk stratification in a particular patient. Modern classification approach with the definition of the stage of gastritis determines the need, activities and frequency of dynamic monitoring of a patient. However, this attitude to the patient suffering from CG was far from always. The present publication is a literature review describing the key milestones in the history of CG research, from the description of the first observations of inflammation of the gastric mucosa, assessment of gastritis as a predominantly functional disease, to the advent of endoscopy of the upper digestive tract and diagnostic gastric biopsy, assessment of the role of Helicobacter pylori infection in progression of inflammatory changes to atrophy, intestinal metaplasia, dysplasia and GC.

When Waldenström macroglobulinemia hits the kidney: Description of a case series and management of a "rare in rare" scenario.

BACKGROUND: Renal injury related to Waldenström macroglobulinemia (WM) occurs in approximately 3% of patients. Kidney biopsy is crucial to discriminate between distinct histopathological entities such as glomerular (amyloidotic and non-amyloidotic), tubulo-interstitial and non-paraprotein mediated renal damage. In this context, disease characterization, management, relationship between renal, and hematological response have been poorly explored. We collected clinical, genetic and laboratory data of seven cases of biopsy-proven renal involvement by WM managed at our academic center and focused on three cases we judged paradigmatic discussing their histopathological patterns, clinical features, and therapeutic options. CASE: In this illustrative case series, we confirm that serum creatinine levels and 24 h proteinuria are parameters that when altered should prompt the clinical suspicion of WM-related renal involvement, even if at present there are not precise cut-off levels recommending the execution of a renal biopsy. In our series AL Amyloidosis (n = 3/7) and tubulo-interstitial infiltration by lymphoma cells (n = 3/7) were the two more represented entities. BTKi did not seem to improve renal function (Case 1), while bortezomib-based regimens demonstrated a beneficial activity on the hematological and organ response, even when used as second-line therapy after chemoimmunotherapy (Case 3) and also with coexistence of anti-MAG neuropathy (Case 2). In case of poor response to bortezomib, standard chemoimmunotherapy (CIT), such as rituximab-bendamustine, represents an effective option (Case 1, 6, and 7). In our series, CIT generates durable responses more frequently in cases with amyloidogenic renal damage (Case 1, 5, and 7). CONCLUSION: In this illustrative case series, we confirm that serum creatinine levels and 24 h proteinuria are parameters that when altered should prompt the clinical suspicion of WM-related renal involvement, even if at present there are not precise cut-off levels recommending the execution of a renal biopsy. Studies with higher numerosity are needed to better clarify the pathological and clinical features of renal involvement during WM and to determine the potential benefit of different therapeutic regimens according to the histopathological subtypes.

Circulating immunome fingerprint in eosinophilic esophagitis is associated with clinical response to proton pump inhibitor treatment.

Objectives: The aim of the study was to characterize the circulating immunome of patients with EoE before and after proton pump inhibitor (PPI) treatment in order to identify potential non-invasive biomarkers of treatment response. Methods: PBMCs from 19 healthy controls and 24 EoE patients were studied using a 39-plex spectral cytometry panel. The plasmacytoid dendritic cell (pDC) population was differentially characterized by spectral cytometry analysis and immunofluorescence assays in esophageal biopsies from 7 healthy controls and 13 EoE patients. Results: Interestingly, EoE patients at baseline had lower levels of circulating pDC compared with controls. Before treatment, patients with EoE who responded to PPI therapy had higher levels of circulating pDC and classical monocytes, compared with non-responders. Moreover, following PPI therapy pDC levels were increased in all EoE patients, while normal levels were only restored in PPI-responding patients. Finally, circulating pDC levels inversely correlated with peak eosinophil count and pDC count in esophageal biopsies. The number of tissue pDCs significantly increased during active EoE, being even higher in non-responder patients when compared to responder patients pre-PPI. pDC levels decreased after PPI intake, being further restored almost to control levels in responder patients post-PPI. Conclusions: We hereby describe a unique immune fingerprint of EoE patients at diagnosis. Moreover, circulating pDC may be also used as a novel non-invasive biomarker to predict subsequent response to PPI treatment.

Radiological and Not Clinical Variables Guide the Surgical Plan in Patients with Glioblastoma.

Background and Purpose: The extent of resection is the most important prognostic factor in patients with glioblastoma. However, the factors influencing the decision to perform a biopsy instead of maximal resection have not been clearly established. The aim of this study was to analyze the factors associated with the intention to achieve maximal resection in glioblastoma patients. Methods: A retrospective single-center case-series analysis of patients with a new diagnosis of glioblastoma was performed. Patients were distributed into two groups: the biopsy (B) and complete resection (CR) groups. To identify factors associated with the decision to perform a B or CR, uni- and multivariate binary logistic regression analyses were performed. Cox regression analysis was also performed in the B and CR groups. Results: Ninety-nine patients with a new diagnosis of glioblastoma were included. Sixty-eight patients (68.7%) were treated with CR. Ring-enhancement and edema volume on presurgical magnetic resonance imaging were both associated with CR. Corpus callosum involvement and proximity to the internal capsule were identified as factors associated with the decision to perform a biopsy. In the multivariate analysis, edema volume (OR = 1.031; p = 0.002) and proximity to the internal capsule (OR = 0.104; p = 0.001) maintained significance and were considered independent factors. In the survival analysis, only corpus callosum involvement (HR = 2.055; p = 0.035) and MGMT status (HR = 0.484; p = 0.027) presented statistical significance in the CR group. Conclusions: The volume of edema and proximity to the internal capsule were identified as independent factors associated with the surgical decision. The radiological evaluation and not the clinical situation of the patient influences the decision to perform a biopsy or CR.

Combination of prostate volume and apparent diffusion coefficient can stratify patients with a PI-RADS score of 3 to reduce unnecessary prostate biopsies.

BACKGROUND: Nowadays, there are many patients who undergo unnecessary prostate biopsies after receiving a prostate imaging reporting and data system (PI-RADS) score of 3. Our purpose is to identify cutoff values of the prostate volume (PV) and minimum apparent diffusion coefficient (ADCmin) to stratify those patients to reduce unnecessary prostate biopsies. METHODS: Data from 224 qualified patients who received prostate biopsies from January 2019 to June 2023 were collected. The Mann-Whitney U test was used to compare non-normal distributed continuous variables, which were recorded as median (interquartile ranges). The correlation coefficients were calculated using Spearman's rank correlation analysis. Categorical variables are recorded by numbers (percentages) and compared by χ2 test. Both univariate and multivariate logistic regression analysis were used to determine the independent predictors. The receiver-operating characteristic curve and the area under the curve (AUC) were used to evaluate the diagnostic performance of clinical variables. RESULTS: Out of a total of 224 patients, 36 patients (16.07%) were diagnosed with clinically significant prostate cancer (csPCa), whereas 72 patients (32.14%) were diagnosed with any grade prostate cancer. The result of multivariate analysis demonstrated that the PV (p < 0.001, odds ratio [OR]: 0.952, 95% confidence interval [95% CI]: 0.927-0.978) and ADCmin (p < 0.01, OR: 0.993, 95% CI: 0.989-0.998) were the independent factors for predicting csPCa. The AUC values of the PV and ADCmin were 0.779 (95% CI: 0.718-0.831) and 0.799 (95% CI: 0.740-0.849), respectively, for diagnosing csPCa. After stratifying patients by PV and ADCmin, 24 patients (47.06%) with "PV < 55 mL and ADCmin < 685 µm2/s" were diagnosed with csPCa. However, only one patient (1.25%) with PV ≥ 55 mL and ADCmin ≥ 685 µm2/s were diagnosed with csPCa. CONCLUSIONS: In this study, we found the combination of PV and ADCmin can stratify patients with a PI-RADS score of 3 to reduce unnecessary prostate biopsies. These patients with "PV ≥ 55 mL and ADCmin ≥ 685 µm2/s" may safely avoid prostate biopsies.

Seeing through the density of dense deposit disease.

Little is known about what constitutes the dense deposits of dense deposit disease (DDD), apart from components of the complement pathway. This study presents the novel finding that large accumulations of apolipoprotein E are present in the deposits of DDD, as revealed by mass spectroscopy and confirmed by both confocal microscopy and immunohistochemistry. The findings suggest a new modality for diagnosis of DDD and introduce potential new mechanisms for understanding DDD pathophysiology.

[Salivary gland disorder: consider IgG4-related disease]. / Speekselklierafwijking: denk aan IgG4-gerelateerde ziekte.

A 73-year-old man was presented with painless, bilateral swelling of the submandibular salivary glands and unilateral swelling of the parotid gland on the right side, and complaints of dry mouth. A parotid biopsy was taken and a serologic exam was carried out, resulting in the diagnosis of IgG4-related disease. IgG4-related disease is a rare systemic disorder that can cause symptoms in the head and neck region. Usually there are complaints of bilateral, painless swelling of the submandibular, parotid and/or lacrimal glands, with or without complaints of dryness of the mouth and eyes.

Microenvironment-induced restoration of cohesive growth associated with focal activation of P-cadherin expression in lobular breast carcinoma metastatic to the colon.

Invasive lobular carcinoma (ILC) is a special breast cancer type characterized by noncohesive growth and E-cadherin loss. Focal activation of P-cadherin expression in tumor cells that are deficient for E-cadherin occurs in a subset of ILCs. Switching from an E-cadherin deficient to P-cadherin proficient status (EPS) partially restores cell-cell adhesion leading to the formation of cohesive tubular elements. It is unknown what conditions control EPS. Here, we report on EPS in ILC metastases in the large bowel. We reviewed endoscopic colon biopsies and colectomy specimens from a 52-year-old female (index patient) and of 18 additional patients (reference series) diagnosed with metastatic ILC in the colon. EPS was assessed by immunohistochemistry for E-cadherin and P-cadherin. CDH1/E-cadherin mutations were determined by next-generation sequencing. The index patient's colectomy showed transmural metastatic ILC harboring a CDH1/E-cadherin p.Q610* mutation. ILC cells displayed different growth patterns in different anatomic layers of the colon wall. In the tunica muscularis propria and the tela submucosa, ILC cells featured noncohesive growth and were E-cadherin-negative and P-cadherin-negative. However, ILC cells invading the mucosa formed cohesive tubular elements in the intercryptal stroma of the lamina propria mucosae. Inter-cryptal ILC cells switched to a P-cadherin-positive phenotype in this microenvironmental niche. In the reference series, colon mucosa infiltration was evident in 13 of 18 patients, one of which showed intercryptal EPS and conversion to cohesive growth as described in the index patient. The large bowel is a common metastatic site in ILC. In endoscopic colon biopsies, the typical noncohesive growth of ILC may be concealed by microenvironment-induced EPS and conversion to cohesive growth.

Context matters: Tumor microenvironments impact cellular therapy success.

In a recent publication, Locke et al. present data from pretreatment tumor biopsies taken on the ZUMA-7 trial. Their results identify tumor microenvironment (TME) contexts and level of CD19 expression as prognostic indicators for responses to axicabtagene ciloleucel (axi-cel).