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INTRODUCTION: The follow-up findings of patients who underwent prostate biopsy for prostate image reporting and data system (PIRADS) 4 or 5 multiparametric magnetic resonance imaging (mpMRI) findings and had benign histology were retrospectively reviewed. METHODS: There were 190 biopsy-naive patients. Patients with at least 12 months of follow-up between 2012 and 2023 were evaluated. All MRIs were interpreted by two very experienced uroradiologists. Of the patients, 125 had either cognitive or software fusion MR-targeted biopsies with 4 + 8/10 cores. The remaining 65 patients had in-bore biopsies with 4-5 cores. Prostate-specific antigen (PSA) levels below 4 ng/mL were defined as PSA regression following biopsy. PIRADS 1-3 lesions on new MRI images were classified as MRI regression. RESULTS: Median patient age and PSA were 62 (39-82) years and six (0.4-33) ng/mL, respectively, at the initial work-up. During a median follow-up period of 44 months, 37 (19.4%) patients were lost to follow-up. Of the remaining 153 patients, 82 (53.6%) had persistently high PSA. Among them, 72 (87.8%) had repeat mpMRI within 6-24 months which showed regressive findings (PIRADS 1-3) in 53 patients (73.6%) and PIRADS 4-5 index lesion persistence in 19 cases (26.4%). The latter group was recommended to have rebiopsy. Of these 19 patients, 16 underwent MRI-targeted rebiopsy. Prostate cancer was diagnosed in six (37.5%) patients and of these four (25%) were clinically significant (>Grade Group 1). Totally, clinically significant prostate cancer was detected in 4/153 (2.6%) patients followed up. CONCLUSION: Patients should be warned against the relative relaxing effect of a negative biopsy after identification of PIRADS 4-5 index lesion. While PSA decrease was observed in many patients during follow-up, persistent MRI findings were present in nearly a quarter of patients with persistently high PSA. A rebiopsy is warranted in these patients, with significant prostate cancer diagnosed in a quarter of patients with rebiopsy.
Subject(s)
Multiparametric Magnetic Resonance Imaging , Prostate-Specific Antigen , Prostatic Neoplasms , Humans , Male , Middle Aged , Aged , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Multiparametric Magnetic Resonance Imaging/methods , Retrospective Studies , Adult , Aged, 80 and over , Prostate-Specific Antigen/blood , Prostate/pathology , Prostate/diagnostic imaging , Image-Guided Biopsy/methods , Follow-Up StudiesABSTRACT
BACKGROUND: Nijmegen breakage syndrome (NBS) is an autosomal recessive DNA repair disorder that manifests through increased genomic instability, malignancy, and cellular and humoral immunodeficiencies. The prognosis for NBS patients is poor due to their increased susceptibility to fatal infections and lymphoproliferative malignancies. Currently, there is no specific treatment for NBS, though allogeneic hematopoietic stem cell transplantation (HSCT) has been performed and documented as case series to demonstrate the utility of transplantation. METHODS: A 14-year-old girl with NBS and haploidentical HSCT from her older brother due to recurrent lung infection was referred for liver transplantation (LT) due to liver cirrhosis, hepatopulmonary syndrome (HPS), and suspicion of liver malignancy. It was decided to perform LT using the living donor who had previously donated for HSCT. RESULTS: Living donor left lobe LT was successfully performed from her brother. The patient experienced no complications in the early postoperative period and was discharged on the seventh postoperative day. Pathological examination of extracted liver has shown "intermediate cell carcinoma" in two foci. After 1 year LT, the patient has had an uneventful course in terms of LT complications and infection, with minimal immunosuppression. CONCLUSIONS: NBS patients have an increased prevalence of malignancies, including primary hepatic malignancy, but most are managed medically or with limited resections. Transplantation in these patients can be curative for hepatic malignancy with a favorable safety profile.
Subject(s)
Hepatopulmonary Syndrome , Liver Neoplasms , Liver Transplantation , Nijmegen Breakage Syndrome , Humans , Adolescent , Female , Liver Neoplasms/surgery , Nijmegen Breakage Syndrome/complications , Hepatopulmonary Syndrome/surgery , Hepatopulmonary Syndrome/etiology , Hepatopulmonary Syndrome/therapy , Bone Marrow Transplantation/adverse effects , Living DonorsABSTRACT
Clear cell Renal Cell Carcinoma (ccRCC) is among the 10 most common cancers in both men and women and causes more than 140,000 deaths worldwide every year. In order to elucidate the underlying molecular mechanisms orchestrated by phosphorylation modifications, we performed a comprehensive quantitative phosphoproteomics characterization of ccRCC tumor and normal adjacent tissues. Here, we identified 16,253 phosphopeptides, of which more than 9000 were singly quantified. Our in-depth analysis revealed 600 phosphopeptides to be significantly differentially regulated between tumor and normal tissues. Moreover, our data revealed that significantly up-regulated phosphoproteins are associated with protein synthesis and cytoskeletal re-organization which suggests proliferative and migratory behavior of renal tumors. This is supported by a mesenchymal profile of ccRCC phosphorylation events. Our rigorous characterization of the renal phosphoproteome also suggests that both epidermal growth factor receptor and vascular endothelial growth factor receptor are important mediators of phospho signaling in RCC pathogenesis. Furthermore, we determined the kinases p21-activated kinase 2, cyclin-dependent kinase 1 and c-Jun N-terminal kinase 1 to be master kinases that are responsible for phosphorylation of many substrates associated with cell proliferation, inflammation and migration. Moreover, high expression of p21-activated kinase 2 is associated with worse survival outcome of ccRCC patients. These master kinases are targetable by inhibitory drugs such as fostamatinib, minocycline, tamoxifen and bosutinib which can serve as novel therapeutic agents for ccRCC treatment.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Male , Humans , Female , Carcinoma, Renal Cell/genetics , CDC2 Protein Kinase/metabolism , p21-Activated Kinases/metabolism , Vascular Endothelial Growth Factor A/metabolism , Phosphopeptides/metabolism , Cell Line, Tumor , Kidney Neoplasms/genetics , Signal Transduction , Cell Proliferation , Gene Expression Regulation, NeoplasticABSTRACT
OBJECTIVES: We aimed to modify the Briganti 2019 nomogram and to test whether it is valid for patients who were diagnosed with prostate cancer through in-bore prostate biopsies. METHODS: Data for 204 patients with positive multiparametric prostate MRI and prostate cancer identified either by mpMRI-cognitive/software fusion or in-bore biopsy and who underwent robot-assisted radical prostatectomy and extended pelvic lymph node dissection between 2012 and 2023 were retrospectively analyzed. The Briganti 2019 nomogram was applied to the mpMRI-cognitive/software fusion biopsy group (142 patients) in the original form, and then, two modifications were tested for the targeted component. Original and modified scores were compared. These modifications were adapted for the in-bore biopsy group (62 patients). The final histopathologic stage was regarded as the gold standard. RESULTS: Nodal metastases were identified in 18/142 (12.6%) of mpMRI-cognitive/software fusion biopsy patients and 8/62 (12.9%) of the in-bore biopsy patients. In the mpMRI-cognitive/software fusion biopsy group, tumor size/core size (%) of targeted biopsy cores and positive core percentage on systematic biopsy were significant parameters for lymph node metastasis based on univariate logistic regression analyses (p < 0.05). With the modifications of these parameters for the in-bore biopsy group, V1 modification of the Briganti 2019 nomogram provided 100% sensitivity and 31.5% specificity (AUC:0.627), while V2 modification provided 75% sensitivity and 46.3% specificity (AUC:0.645). CONCLUSIONS: Briganti 2019 nomogram may be modified by utilizing tumor size/core size (%) for targeted biopsy cores instead of positive core percentage on systematic biopsy or by not taking both parameters into consideration to detect node metastasis risk of patients diagnosed with in-bore biopsies.
ABSTRACT
Adenosine deaminase (ADA) deficiency is one of the most prevalent forms of severe combined immunodeficiency and results in the accumulation of toxic substrates which creates a systemic metabolic disease. It predisposes patients to the development of malignancies, most commonly lymphoma. We report an 8-month-old infant with ADA deficient severe combined immunodeficiency who developed progressive liver dysfunction and hepatocellular carcinoma after successful hematopoietic stem cell transplantation. This is the first case report of an ADA-deficient patient who presented with hepatocellular carcinoma and gives an insight into the complex etiology that can lie behind liver dysfunction in these patients.
Subject(s)
Carcinoma, Hepatocellular , Hematopoietic Stem Cell Transplantation , Liver Neoplasms , Severe Combined Immunodeficiency , Infant , Humans , Severe Combined Immunodeficiency/complications , Severe Combined Immunodeficiency/therapy , Adenosine Deaminase , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/adverse effectsABSTRACT
PURPOSE: In this retrospective study, we aimed to determine the safe surgical limit for excision of pterygium tissue. Therefore, we aimed to prevent excessive or incomplete normal conjunctival tissue excision during surgery in the coming years. METHODS: Autografted pterygium surgery was performed between January 2015 and April 2016, and the excised pterygium tissue was examined histopathologically. The files of 44 patients, who had not previously undergone any ocular surgery, who did not have an inflammatory disease and who continued to be checked for at least 1 year, were retrospectively examined. The distance (P-DSEM) from the excised pterygium tissue to the surgical excision margin was measured by a pathologist. Postoperative recurrence rates were evaluated according to this value. In this way, the clean surgical margin was determined. RESULTS: The mean age of the participants was 44.77 ± 12.70, and the mean follow-up time was 55.61 ± 16.38 months. Recurrence developed in 5 out of 44 patients (11.4%). The average recurrence duration was 51 ± 13.87 days. Distance to the average surgical margin was 3.88 ± 0.91 mm. The surgical distances of 5 patients with recurrence were 2, 2.5, 2, 3, and 3 mm, respectively. It was determined that recurrence was less as the distance (P-DSEM) from the tissue to the surgical excision margin increased (p = 0.001). CONCLUSIONS: We found that the recurrence rate in pterygium surgery was linked to the clean surgical margin. When planning pterygium surgery, we believe that determining the amount of tissue to be excised before surgery will reduce recurrence rates.
ABSTRACT
The advancing edge profile is a powerful determinant of tumor behavior in many organs. In this study, a grading system assessing the tumor-host interface was developed and tested in 181 pancreatic neuroendocrine tumors (PanNETs), 63 of which were <=2 cm. Three tumor slides representative of the spectrum (least, medium, and most) of invasiveness at the advancing edge of the tumor were selected, and then each slide was scored as follows. Well-demarcated/encapsulated, 1 point; Mildly irregular borders and/or minimal infiltration into adjacent tissue, 2 points; Infiltrative edges with several clusters beyond the main tumor but still relatively close, and/or satellite demarcated nodules, 3 points; No demarcation, several cellular clusters away from the tumor, 4 points; Exuberantly infiltrative pattern, scirrhous growth, dissecting the normal parenchymal elements, 5 points. The sum of the rankings on the three slides was obtained. Cases with scores of 3-6 were defined as "non/minimally infiltrative" (NI; n = 77), 7-9 as "moderately infiltrative" (MI; n = 68), and 10-15 as "highly infiltrative" (HI; n = 36). In addition to showing a statistically significant correlation with all the established signs of aggressiveness (grade, size, T-stage), this grading system was found to be the most significant predictor of adverse outcomes (metastasis, progression, and death) on multivariate analysis, more strongly than T-stage, while Ki-67 index did not stand the multivariate test. As importantly, cases <=2 cm were also stratified by this grading system rendering it applicable also to this group that is currently placed in "watchful waiting" protocols. In conclusion, the proposed grading system has a strong, independent prognostic value and therefore should be considered for integration into routine pathology practice after being evaluated in validation studies with larger series.
Subject(s)
Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Neoplasm Grading , Neuroendocrine Tumors/pathology , Pancreatic Neoplasms/pathology , PrognosisABSTRACT
BACKGROUND: To investigate if remote ischemic preconditioning (RIPC) can offer any renoprotective value by counteracting the deleterious effect of partial nephrectomy (PN) under warm ischemia on renal function. METHODS: Four groups, each with 5 Wistar albino rats, were constructed; RIPC + PN, PN, RIPC and sham. Right nephrectomy was performed to constitute a solitary kidney model. RIPC denoted sequential clamping/declamping of the femoral artery/vein complex. PN was performed under warm-ischemia following RIPC. Blood samples were collected on multiple occasions until euthanasia on day 7. Immunoassays were conducted to measure the serum and tissues levels of kidney injury markers. Kidneys were examined histologically and morphometric analyzes were performed using digital scanning. RESULTS: IL-33 levels did not differ significantly between the groups. Serum levels of KIM-1, NGAL, and aldose reductase in RIPC + PN, PN and RIPC groups were significantly lower than that of sham group. Tissue biomarker levels were similar across groups. The observed trend in mean necrosis area of PN group was higher than that of RIPC + PN group (p > 0.05). The transitional zone between necrosis and healthy tissue showed a trend towards increasing width in the rats subjected to RIPC before PN vs. those who underwent PN without RIPC (p > 0.05). CONCLUSION: RIPC failed to counteract the renal functional consequences of PN under warm ischemia in a solitary kidney animal model. The supportive but marginal histological findings in favor of RIPC's renoprotective potential were not supplemented with the changes in serum and tissue biomarker levels.
Subject(s)
Cell Adhesion Molecules/analysis , Ischemic Preconditioning/methods , Kidney , Lipocalin-2/analysis , Nephrectomy , Reperfusion Injury , Aldehyde Reductase/analysis , Animals , Biomarkers/analysis , Disease Models, Animal , Kidney/metabolism , Kidney/pathology , Kidney/physiopathology , Kidney Function Tests , Nephrectomy/adverse effects , Nephrectomy/methods , Rats , Rats, Wistar , Reperfusion Injury/blood , Reperfusion Injury/etiology , Reperfusion Injury/pathology , Treatment Outcome , Warm Ischemia/methodsABSTRACT
OBJECTIVE. The objective of our study was to evaluate the relationship between the tumor-capsule contact length, defined as tumor contact length (TCL), and extraprostatic extension (EPE) using the MRI-based TCL measurements and the real TCL measurements from pathology and to determine whether the International Society of Urological Pathology (ISUP) grade group of the tumors influenced this relationship. MATERIALS AND METHODS. In this retrospective study, we reviewed prostate multiparametric MRI (mpMRI) studies performed between 2012 and 2018 of 1576 patients and found that 134 patients also underwent radical prostatectomy (RP) after mpMRI. Finally, 86 patients with index lesions in contact with the prostate capsule in RP specimens were enrolled in the study. ROC analysis was used to evaluate the cutoff values of TCLs measured at pathology and TCLs measured on MRI in terms of EPE according to ISUP grade groups. RESULTS. There was no statistically significant cutoff value for pathology-based TCL measurements in individual ISUP grade groups and subgroups. Although not statistically significant, pathology-based TCL cutoff values decreased (from 21.0 to 11.0 mm) as ISUP grade group increased in terms of EPE positivity. When the relationship between MRI-based TCL measurements and EPE was considered, statistically significant cutoff values (range, 14.5-16.6 mm) could be determined in many groups and subgroups with low ISUP grades (sensitivity, 66.7-100%; specificity, 52.8-93.0%; p = 0.006-0.042). However, no statistically significant cutoff value was found for high ISUP grades. CONCLUSION. ISUP grade groups may have an effect on the TCL-EPE relationship. When the MRI-based TCL and EPE relationship is evaluated independent of ISUP grade group, a cutoff value around 15-16 mm may be usable to predict EPE.
Subject(s)
Magnetic Resonance Imaging/methods , Neoplasm Invasiveness/diagnostic imaging , Neoplasm Invasiveness/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Aged , Contrast Media , Diffusion Magnetic Resonance Imaging , Humans , Image Interpretation, Computer-Assisted , Image-Guided Biopsy , Male , Middle Aged , Neoplasm Grading , Prostatectomy , Prostatic Neoplasms/surgery , Retrospective Studies , Sensitivity and SpecificityABSTRACT
OBJECTIVE: To analyze clinicopathologic characteristics of upper gastrointestinal leiomyomas and to determine the distribution and immunohistochemical features of interstitial cells of Cajal, in order to designate whether they can cause diagnostic challenges. MATERIALS AND METHODS: Twenty-four upper gastrointestinal leiomyomas (14 esophagus, 10 stomach) were retrieved. CD117, DOG-1 and muscle markers were performed. The staining was analyzed based on the distribution and percentage. Interstitial cells of Cajal were distinguished based on their positivity for both CD117 and DOG-1 immunohistochemistry, along with their morphological features. RESULTS: Mean age of patients was 49â¯years, M/F ratio was 2.4. Patients with gastric leiomyomas were significantly younger than those with esophageal leiomyomas (41.5 vs. 54.3, pâ¯=â¯0.012). Histologically, leiomyomas were similar to their endometrial counterpart. Immunohistochemically, all tumors had strong/diffuse positivity for muscle markers. CD117 highlighted mast cells in all cases. Three cases had prominently increased mast cells. Both CD117 and DOG-1 also highlighted interstitial cells of Cajal in 24/24 (100%) of cases. Interstitial cells of Cajal were distributed in variable proportions, from focal to homogenous. In one case, they constituted 50% of tumor cells. In 16 cases, the distribution was homogenous. Superficial leiomyomas (nâ¯=â¯3) had only focal CD117 and DOG-1 positivity. CONCLUSION: Upper gastrointestinal leiomyomas harbor expression of CD117 and DOG-1 in entrapped/colonized interstitial cells of Cajal, which can cause a potential pitfall in the differential diagnosis, especially in cases that show prominent immunohistochemical positivity. Evaluation of the immunohistochemistry can be exceptionally challenging in small biopsy/cytology specimens. Careful histologic evaluation of the tumor as well as the recognition of interstitial cells of Cajal will help the pathologist render the accurate diagnosis.
Subject(s)
Anoctamin-1/metabolism , Gastrointestinal Stromal Tumors/pathology , Interstitial Cells of Cajal/metabolism , Leiomyoma/metabolism , Neoplasm Proteins/metabolism , Proto-Oncogene Proteins c-kit/metabolism , Upper Gastrointestinal Tract/pathology , Adolescent , Adult , Aged , Diagnosis, Differential , Esophageal Neoplasms/metabolism , Esophageal Neoplasms/pathology , Female , Humans , Immunohistochemistry/methods , Interstitial Cells of Cajal/pathology , Leiomyoma/pathology , Male , Middle Aged , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Young AdultABSTRACT
OBJECTIVE: Lymph node metastasis occurs in a subset of papillary microcarcinoma patients. We aimed to analyze the differences between metastatic and non-metastatic papillary microcarcinomas in order to identify a high-risk subgroup that is likely to require more aggressive treatment. MATERIALS AND METHODS: 126 thyroidectomies with lymph node dissections (central⯱â¯lateral), diagnosed as papillary microcarcinoma, were reviewed. RESULTS: Mean age of 126 patients (F/Mâ¯=â¯3.3) was 42â¯years. Mean size of the largest tumor was 7â¯mm. Classical was the most frequently (89%) encountered subtype. Multiple histologic subtypes co-occurred in 19%. Lymphovascular invasion was present in 16% (nâ¯=â¯20). 55 (44%) and 71 (56%) cases were unifocal and multifocal, respectively. 90 cases (71%) were non-encapsulated with overall infiltrative tumor borders, whereas in 36 cases (29%), the tumor had a well-defined capsule. Among those, 23 (64%) had tumor capsule invasion. 47 (37%) cases had metastasis in lymph nodes. In univariate analysis, metastasis was associated with tumor size of >5â¯mm (pâ¯=â¯0.02), tumor burden of >5 mm (pâ¯=â¯0.03), lymphovascular invasion (pâ¯=â¯0.02) and non-encapsulation (pâ¯=â¯0.01). No associations were found regarding sex, age, histologic subtype, lymphocytic thyroiditis, tumor capsule invasion (in capsulated tumors), laterality and multifocality (pâ¯>â¯0.05). In multivariate analysis, lymphovascular invasion (pâ¯=â¯0.01, ORâ¯=â¯3.97, 95% CI 1.35-11.67), tumor size >0.5â¯cm (pâ¯=â¯0.031, ORâ¯=â¯2.92, 95% CI 1.10-7.71) and non-encapsulation (pâ¯=â¯0.033, ORâ¯=â¯2.85, 95% CI 1.08-7.51) were independent risk factors. CONCLUSION: Size (largest tumor or sum of all foci) of >5 mm, non-encapsulation and lymphovascular invasion were independent predictors of LNM in PMs. Unifocal tumors metastasize the same as multifocal tumors, suggestive of the contribution of other factors. Patients with sporadically resected microcarcinomas should be carefully followed-up, especially those that harbor risk factors in histology.
Subject(s)
Carcinoma, Papillary/pathology , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Thyroid Neoplasms/pathology , Adolescent , Adult , Aged , Carcinoma, Papillary/surgery , Female , Humans , Lymph Node Excision/methods , Lymph Node Excision/statistics & numerical data , Lymph Nodes/surgery , Male , Middle Aged , Neoplasm Invasiveness , Predictive Value of Tests , Retrospective Studies , Risk Factors , Thyroidectomy/methods , Thyroidectomy/statistics & numerical data , Tumor Burden , Young AdultABSTRACT
PURPOSE: To investigate the performance of computed tomography (CT) in the local staging of colon cancer in different segments, with emphasis on parameters that have been found to be significant for rectal cancer, namely, extramural venous invasion (EMVI) and tumor deposits (TDs). METHODS: CT and pathology data from 137 patients were independently reviewed by radiology and pathology teams. The performance of CT in categorizing a given patient into good, versus poor prognostic groups was assessed for each segment, as well as the presence of lymph nodes (LNs), TDs and EMVIs. Discordant cases were re-evaluated to determine potential sources of error. Elastic stain was applied for EMVI discordance. RESULTS: The T staging accuracy was 80.2%. For T stage stratification, CT performed slightly better in the left colon, and the lowest accuracy was in the transverse colon. Under-staging was more common (in 12.4%), and most of the mis-staged cases were in sigmoid colon. According to the first comprehensive correlative analysis, the sensitivity, specificity, and accuracy of CT for detecting TDs were found to be 57.9%, 92.4%, 87.6%, respectively. These figures were 44.7%, 72.7%, and 63.5% for LN, and 58.5%, 82.1% and 73% for EMVI. The detection rate was better for multifocal EMVI. The detection rate was also comparable (although substantially underestimated) for LNs, with the half of the LNs missed by CT being < 5 mm. Four patients that were classified as TD by CT, disclosed to be LNs by pathology. Correlative analysis led to refinement of the pathology criteria, with subsequent modifications of the initial reports in 13 (9.5%) patients. CONCLUSION: Overall, CT performed well in the evaluation of colon cancer, as did TD and EMVI. It is advisable to include these parameters in CT-based staging. Radiologists should be aware of the pitfalls that occur more commonly in different segments.
Subject(s)
Colonic Neoplasms , Neoplasm Invasiveness , Neoplasm Staging , Sensitivity and Specificity , Tomography, X-Ray Computed , Humans , Colonic Neoplasms/diagnostic imaging , Colonic Neoplasms/pathology , Male , Female , Aged , Middle Aged , Tomography, X-Ray Computed/methods , Aged, 80 and over , Adult , Retrospective Studies , Contrast Media , Prognosis , Lymphatic Metastasis/diagnostic imagingABSTRACT
A type of cholangiocarcinoma (CCA) characterized by peculiar histologic patterns and underlying adenofibromatous lesions has been reported in the literature mostly as individual case reports. This study aims to further clarify the defining characteristics of this spectrum of lesions. Clinicopathologic analysis of 8 biliary tumors with tubulocystic architecture arising in the background of adenofibroma-type lesions was performed. Three of these were also investigated with next-generation sequencing with a 174 genes panel. The patients were 5 males and 3 females, with a mean age of 64.6. All tumors were intrahepatic except for one perihilar that protruded into soft tissues. The mean size was 4.4 cm. At histology, all cases showed a peculiar and cytologically bland tubulocystic pattern that closely resembled tubulocystic-type kidney cancers, including back-to-back microcystic units that formed relatively demarcated nodules, and occurring in the background of adenofibromatous lesions. One case showed perineural invasion by otherwise deceptively benign-appearing microcystic structures, one had areas transitioning to intraductal tubulopapillary neoplasm, and 3 cases harbored more conventional small-duct CCA foci. In those 3 cases, both the tubulocystic and conventional CCA components were investigated by next-generation sequencing separately, and they shared the molecular alterations, including recurrent mutations in chromatin remodeling genes, such as ARID1A , BAP1 , and PBRM1 , and the actionable FGFR2-MCU fusion gene. In the limited follow-up, all but one were alive and free of disease after surgical resection. In conclusion, we described a distinct entity of CCA with specific histo-molecular features, for which we propose the designation of tubulocystic carcinoma of bile ducts.
Subject(s)
Adenofibroma , Bile Duct Neoplasms , Biomarkers, Tumor , Cholangiocarcinoma , High-Throughput Nucleotide Sequencing , Humans , Male , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/surgery , Female , Middle Aged , Cholangiocarcinoma/genetics , Cholangiocarcinoma/pathology , Cholangiocarcinoma/surgery , Aged , Adenofibroma/pathology , Adenofibroma/genetics , Adenofibroma/surgery , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis , Mutation , Bile Ducts, Intrahepatic/pathology , Bile Ducts, Intrahepatic/surgery , PhenotypeABSTRACT
The guidelines recently recognized the intra-ampullary papillary tubular neoplasm (IAPN) as a distinct tumor entity. However, the data on IAPN and its distinction from other ampullary tumors remain limited. A detailed clinicopathologic analysis of 72 previously unpublished IAPNs was performed. The patients were: male/female=1.8; mean age=67 years (range: 42 to 86 y); mean size=2.3 cm. Gross-microscopic correlation was crucial. From the duodenal perspective, the ampulla was typically raised symmetrically, with a patulous orifice, and was otherwise covered by stretched normal duodenal mucosa. However, in 6 cases, the protrusion of the intra-ampullary tumor to the duodenal surface gave the impression of an "ampullary-duodenal tumor," with the accurate diagnosis of IAPN established only by microscopic correlation illustrating the abrupt ending of the lesion at the edge of the ampulla. Microscopically, the preinvasive component often revealed mixed phenotypes (44.4% predominantly nonintestinal). The invasion was common (94%), typically small (mean=1.2 cm), primarily pancreatobiliary-type (75%), and showed aggressive features (lymphovascular invasion in 66%, perineural invasion in 41%, high budding in 30%). In 6 cases, the preinvasive component was pure intestinal, but the invasive component was pancreatobiliary. LN metastasis was identified in 42% (32% in those with ≤1 cm invasion). The prognosis was significantly better than ampullary-ductal carcinomas (median: 69 vs. 41 months; 3-year: 68% vs. 55%; and 5-year: 51% vs. 35%, P =0.047). In conclusion, unlike ampullary-duodenal carcinomas, IAPNs are often (44.4%) predominantly nonintestinal and commonly (94%) invasive, displaying aggressive features and LN metastasis even when minimally invasive, all of which render them less amenable to ampullectomy. However, their prognosis is still better than that of the "ampullary-ductal" carcinomas, with which IAPNs are currently grouped in CAP protocols (while IAPNs are kindreds of intraductal tumors of the pancreatobiliary tract, the latter represents the ampullary counterpart of pancreatic adenocarcinoma/cholangiocarcinoma).
Subject(s)
Ampulla of Vater , Common Bile Duct Neoplasms , Humans , Male , Female , Ampulla of Vater/pathology , Aged , Middle Aged , Adult , Aged, 80 and over , Common Bile Duct Neoplasms/pathology , Common Bile Duct Neoplasms/mortality , Common Bile Duct Neoplasms/surgery , Neoplasm Invasiveness , Duodenal Neoplasms/pathology , Carcinoma, Papillary/pathology , Carcinoma, Papillary/surgeryABSTRACT
"Eosinophilic cholecystitis" has been an elusive concept. Around 1050 consecutive cholecystectomies with chronic (CC, n = 895), subacute (SAC, n = 100), and acute cholecystitis (AC, n = 55) were reviewed for eosinophilic infiltration. Eosinophilic hot spots (>40 eosinophils/HPF) were seen in 63% of SAC and 35% of AC (vs. 6% of CC, p < 0.001). Eosinophils were mostly encountered in areas of wall thickening, revealing edema with early collagenization and young tissue-culture-type fibroblasts. However, in ten chronic cholecystitis patients (<1%), prominent eosinophilia with eosinophil-rich foci (>100 eosinophils/HPF) was noted. These ten cases, classified as "eosinophilic cholecystitis", were analyzed further: The patients were relatively young (mean age = 43 years), with a 9:1 female:male ratio. None had blood eosinophilia/eosinophilia syndromes. Although one had ulcerative colitis, others did not have any autoimmune diseases. The mean gallbladder wall thickness was 3.5 mm (vs. 4.2 mm in ordinary CC). In conclusion, eosinophils are a part of especially subacute injuries in the gallbladder. They are typically condensed in the areas of healing and appear to signify a distinctive state of injury in which there are erosions leading to slow/sustained exposure of the mural tissues to the bile contents that induce chemical injury/recruit eosinophils. Eosinophilic cholecystitis is a very uncommon occurrence and appears to be an exaggerated response in allergic patients who are prone to recruit eosinophils in reaction to injury.
ABSTRACT
We evaluated and described the impact of prostatic indocyanine green (ICG) injection on extended pelvic lymph node (LN) dissection (ePLND) in robotic-assisted radical prostatectomy (RARP). Between January 2019 and December 2021, we included consecutive 50 PCa patients who underwent ePLND during RARP with (n = 25) or without (n = 25) prostatic ICG injection. ICG injection was performed during abdominal port placement and robot docking. Pelvic LNs reflecting green color were initially excised and then the template was completed. The outcomes of two groups were compared. Overall, nine (36%) and five (20%) of the patients had metastatic LN involvement in the ICG and non-ICG groups, respectively. Of the 509 dissected LNs in the ICG group, 122 (23.9%) were fluorescence active. 20 LNs (3.9%) were metastatic in this group, 9 (45%) of which were ICG+. 408 LNs were resected on the non-ICG group with 8(1.9%) being metastatic. Eight (88.9%) of nine pN+ patients were florescent positive in the ICG group. Out of six patients with pN+ disease, Ga68 PSMA-PET/CT detected positive LNs preoperatively. In addition to preoperative Ga68 PSMA-PET/CT investigation, ICG-guided ePLND might increase identification and removal of metastatic LNs duirng RARP. Improvements in staging and oncologic outcomes may also be seen in intermediate- and high-risk patients.
Subject(s)
Prostatic Neoplasms , Robotic Surgical Procedures , Robotics , Male , Humans , Robotic Surgical Procedures/methods , Fluorescence , Positron Emission Tomography Computed Tomography , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Lymph Node Excision , Prostatectomy , Indocyanine GreenABSTRACT
BACKGROUND: We aimed to analyze the effect of preoperative risk assessment including Ga-68 PSMA PET and multiparametric magnetic resonance imaging (mpMRI) on nerve sparing practices, positive surgical margin (PSM) rates and oncological outcomes based on a comparison between patients underwent RARP with and without Neurosafe (NS). METHODS: Patients underwent RARP with NS (RARP-NS) or without (RARP-only) NS retrospectively evaluated. Suspicion for extracapsular extension on mpMRI and/or Ga-68 PSMA PET was recorded as i(imaging)T3. NS was performed according to the Martini-Klinik technique. PSM at preserved bundle side were called PSM at region of interest (ROI) while the others were elsewhere. RESULTS: A total of 208 patients (90 in RARP-NS, 118 in RARP-only groups) were included. Preoperatively the RARP-only group showed significantly higher mean PSA (p = .01) and PIRADS 5 (p = .002) findings and had more D'Amico high risk (DAHR) patients (p = .08). The overall PSM rates for pT2 versus pT3 disease were 7.5% versus 21.6 and 15.6% versus 55% in RARP-NS and RARP-only groups, respectively. NS resulted in more bilaterally preserved bundles (81.1% vs. 66.3%) and less PSM at the ROI (3.3% vs. 23.4%) than RARP-only group. NS outperformed RARP-only in all clinical settings had its highest differential benefit in more bilateral nerve sparing and less PSM at ROI in patients with both DAHR and iT3 disease. BCR rates were 2.2% and 2.5% for RARP-NS and RARP only groups, respectively (p = .4). One patient in RARP-NS and 9 in RARP-only groups had PSA persistence (p = .02). CONCLUSION: RARP-NS led to more preserved bundles with less PSM. It was especially useful in DAHR patients with preoperative extracapsular extension suspicion in imaging simultaneously.
ABSTRACT
We analyzed metastatic liver tumors received in the department of pathology in a tertiary care center over a 3-year period. There were 509 metastatic liver tumors; counterintuitively, there were as many resections (235 cases) as biopsies (274 cases). This unexpected finding reflects contemporaneous organ-specific paradigms for diagnosis and management of metastatic liver disease in oncologic practice, and the association of our practice with a National Cancer Institute-designated comprehensive cancer center with expertise and specialization in liver surgery. We receive a large number of resections for metastatic liver tumors because metastasectomy from a variety of primary tumors is associated with improved overall, and in many instances, disease-free, long-term survival. Metastatic colorectal carcinomas, metastatic neuroendocrine tumors, and metastatic gastrointestinal stromal tumors constituted 78% of resections because the largest body of literature and cumulative experience exists for these lesions. In contrast, breast carcinomas and pancreatic carcinomas, which are the next common metastatic liver tumors were biopsied but rarely resected, because metastasectomy is not the standard of care for these tumors. Immunohistochemistry was performed in less than a quarter of the total number of cases (23%), because the primary tumor site was known in the vast majority of cases. Of the 42 cases with unknown primary tumor, it was elucidated in 50% of the cases by immunohistochemical and clinical work-up. Of the cases with known primary tumor, immunohistochemistry was performed mostly in metastatic breast, colon, and lung carcinomas. In these cases, biomarker analyses provided additional information relevant to clinical management.
Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Neuroendocrine Tumors , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/surgery , Humans , Immunohistochemistry , Liver Neoplasms/diagnosis , Liver Neoplasms/pathology , Liver Neoplasms/surgery , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/pathology , Neuroendocrine Tumors/surgery , Tertiary Care CentersABSTRACT
OBJECTIVE: To determine the frequency of granulomatous inflammation within hepatocellular carcinoma (HCC) and its clinicopathologic associations. MATERIAL AND METHOD: Fifty-eight HCCs (51 explants, 3 lobectomies, and 4 segmentectomies) were reviewed. RESULTS: Five (8.6%) cases (F/M=1/4, mean age: 63.6) were identified with granulomas.1/5 had history of neoadjuvant therapy. 4/5 patients presented with early stage (pT1/2). All were well-differentiated (Grade1-2/4). The mean number of tumor foci was 3.6, with a median size of 2.2 cm. All of them had advanced fibrosis. No difference was identified from cases without granulomas (n=53) in terms of prognosis and aforementioned parameters (p > 0.05). Granulomas were mainly concentrated in peripheral parts of the tumors. One case with nodule-in-nodule formation had granulomas lined along the border of the inner nodule. In 2 cases, granulomas were identified in steatohepatitic areas, while another had clear cell change. Only 1 had necrotizing granulomas, none with acid resistant bacilli. Two cases revealed concomitant granulomas in the adjacent liver parenchyma in addition to the tumor stroma. Except for one with a history of tuberculosis, none of the cases had a granulomatous disease. CONCLUSION: This is the largest case series of HCCs with granulomas by far. Our data revealed neither clinicopathologic and prognostic difference nor definite etiology related to granulomas. Yet, association with steatotic and clear tumor cells suggests the role of cytoplasmic content, while distribution of granulomas points to host immune response.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Carcinoma, Hepatocellular/pathology , Granuloma/pathology , Humans , Inflammation , Liver Neoplasms/pathology , Middle AgedABSTRACT
BACKGROUND: The cost-effectiveness and low rate of inadequate sampling with the use of rapid on-site evaluation (ROSE) along with endobronchial ultrasonography (EBUS) is well established. Our aim in this study was to evaluate the correlation of ROSE during EBUS and final cytologic diagnosis and also to see if ROSE might predict the subtype of lung cancer. PATIENTS AND METHODS: All consecutive subjects who attended our clinic between January 2016 and January 2019 for the evaluation of pathologic mediastinal and/or hilar lymph nodes (LNs)/mass using EBUS were enrolled into our prospective study. ROSE was performed in the same operating room with EBUS. ROSE results during EBUS were recorded. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ROSE compared with the final cytologic diagnosis were evaluated. RESULTS: We enrolled 684 LN/mass lesions belonging to 328 patients into this study. When we compared ROSE results and final cytologic diagnosis, these procedures agreed on 91.6% of the LNs (P<0.001). The sensitivity of ROSE and final cytologic diagnosis for granulomatous inflammation was 72.5%, and for lung cancer, it was 89.2% (P<0.001). The sensitivity of ROSE for the adenocarcinoma subtype of lung cancer was 67.7%, and it was 70% for small cell lung cancer. CONCLUSION: ROSE may help to recognize non-small cell lung cancer during EBUS, especially the adenocarcinoma subtype of lung cancer, which will help ensure having sufficient material for molecular analysis.