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AIMS: The current criteria for surgical treatment after endoscopic resection of a pT1 colorectal carcinoma (CRC) are unsatisfactory because nodal involvement is rarely present. This study investigates the correlation between PD-L1 expression and nodal metastasis in pT1 CRCs to enable its use for tailoring surgical treatment after endoscopic removal. METHODS AND RESULTS: Histopathological features of 81 surgically resected pT1 CRC, 19 metastatic and 62 non-metastatic cases were assessed. PD-L1 expression was evaluated by immunohistochemistry (clone 22C3) and independently assessed by two pathologists using tumour proportion score (TPS), combined positive score (CPS) and immune cell score (ICS). The correlation between PD-L1 expression and nodal metastasis, the optimal cut-off values, interobserver agreement and impact upon patients' surgical management were determined. PD-L1 expression in terms of CPS and ICS independently correlated with lymph node metastasis (PD-L1CPS : OR = -2.5, 95% CI = -4.11 to -0.97, P = 0.008 and PD-L1ICS : OR = -1.85, 95% CI = -2.90 to -0.79, P = 0.004) and < 1.2 CPS and <1.3% ICS were identified as the optimal cut-off values to discriminate between metastatic and non-metastatic patients. In our cohort, the implementation of these cut-off values would have avoided a significant rate of unnecessary surgeries in pN0 patients (PD-L1CPS = 43.2; PD-L1ICS = 51.9%). Ultimately, PD-L1 evaluation showed good interpathologist concordance in absolute terms [PD-L1CPS interclass correlation coefficient (ICC) = 0.91; PD-L1ICS ICC = 0.793] and using the identified cut-off values (PD-L1CPS ICC = 0.848; PD-L1ICS ICC = 0.756). CONCLUSIONS: Our study shows that PD-L1 expression is an effective predictor of nodal status and could improve patient selection for surgery after endoscopic removal of pT1 CRCs.
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Antígeno B7-H1 , Neoplasias Colorretais , Humanos , Antígeno B7-H1/metabolismo , Imuno-Histoquímica , Metástase Linfática , Patologistas , Biomarcadores Tumorais , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologiaRESUMO
BACKGROUND AND OBJECTIVES: Italy was severely affected by the severe acute respiratory syndrome coronavirus 2 pandemic. Our Institution, Piedmont's largest tertiary referral center, was designated as a non-COVID-19 hospital and activities were reorganized to prioritize critical services like oncological care. The aim of this study was to investigate the efficacy in preserving the oncological surgical practice at our Institution during the most critical months of the COVID-19 epidemic by analyzing the surgical pathology activity. METHODS: The number of oncological surgical resections submitted to histopathological examination from 9th March 2020 to 8th May 2020 were collected as well staging/grading data and compared with the previous three pre-COVID-19 years (2017-2019). RESULTS: Overall, no decrease was observed for most tumor sites (5/9) while breast resections showed the largest drop (109 vs. 160; -31.9%), although a full recovery was already noticed during the second half of the period. Conversely, the selected control benchmarks showed a sharp decrease (-80.4%). Distribution of pathological TNM stages (or tumor grades for central nervous system tumors) showed no significant differences during the lockdown compared with previous years (p > .05). CONCLUSIONS: The present data suggest the possibility of preserving this cornerstone oncological activity during an evolving public health emergency thanks to a prompt workflow reorganization.
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COVID-19/prevenção & controle , Neoplasias/cirurgia , Patologia Cirúrgica , SARS-CoV-2 , Oncologia Cirúrgica , Humanos , Estadiamento de Neoplasias , Neoplasias/patologia , Encaminhamento e Consulta , Centros de Atenção TerciáriaRESUMO
In thyroid pathology, the great variety of types and the wide range of aggressiveness of thyroid cancers complicate both diagnosis and management. In 2016, a subset of noninvasive encapsulated follicular variant of papillary thyroid carcinoma was reclassified as noninvasive follicular thyroid tumor with papillary-like nuclear features (NIFTP) to reduce overtreatment of this low-risk tumor that follows a benign course after surgery. Starting from a paradigmatic clinical case, in this short review, we will summarize the ultrasonography, cytological, histological and molecular features of this new entity. In the preoperative settings, the recognition of some peculiar elements may only suggest the possibility of a NIFTP, thus favoring a less aggressive surgical approach. However, the diagnosis of NIFTP can only be made after complete resection of the lesion by detecting well-defined inclusion and exclusion histopathological criteria. Since NIFTP is not 'malignant,' surgery may be considered curative with no further treatment or surveillance needed. NIFTP-related issues, including nodule size, multifocality, oncocytic changes, heterogeneous incidence across different geographical areas and its occurrence in the pediatric age, will be discussed.
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Adenocarcinoma Folicular/diagnóstico por imagem , Adenocarcinoma Folicular/genética , Perfil Genético , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/genética , Ultrassonografia/métodos , Núcleo Celular/patologia , Feminino , Geografia , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Período Pré-Operatório , Estudos Retrospectivos , Glândula Tireoide/patologia , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Mucin disfunction is a critical event in the pathogenesis of inflammatory bowel disease (IBD). Although hyper mucinous conditions have a still debated implication in the clinical evolution of this disorder, hyper mucinous villous proliferations were found to have a preneoplastic biologic potential. We studied morphologic and immunophenotypic characteristics of these lesions in ileocolonic resections for IBD to add evidence about the evolutive potential of these lesions in samples with well oriented wall structures. METHODS: Morphologic characteristics of bowel samples from 20 patients resected for IBD and with raised lesions at gross examination were studied and sections from cases with hyper mucinous lesions were stained with the following antibodies: Ki 67, p21, and p27, which were employed to evaluate the characteristics of the proliferative and differentiative activity of the epithelial structures; mismatch repair proteins and p53 have been studied as proteins implicated in carcinogenesis in IBD-affected mucosa; mucins subtypes in hyper mucinous structures were evaluated with MUC-2 and MUC-6. The results in 11 cases of saplings were that they harbored hyper mucinous proliferations. The occurrence of hyper mucinous structures was not related to dysplastic lesions, pseudo pyloric metaplasia, subtype of disease, or activity. In only one of our cases, mild cytologic atypia in the proliferative compartment was detected. Proliferation markers (Ki 67, p53) were expressed in the proliferative compartments of mucosal crypts and antiproliferative proteins p21 and p27 were expressed in differentiated epithelium. MMR proteins expression was limited to the proliferative compartment of the hyper mucinous projections. Mucin subtypes distribution was regular in the epithelium of hyper mucinous proliferations. CONCLUSIONS: The present monocentric retrospective study was conducted on surgical samplings with well oriented crypts. Collected data show that hyper mucinous features are frequent occurrences in raised lesions in IBD patients. In hyper mucinous proliferations of the selected cases, the status of the proliferative cycle, the expression of the proteins most frequently involved in carcinogenetic pathways of mucosa affected by IBD, and the mucins subtypes expression have no evident anomalies. Findings are not consistent with the increased risk of neoplastic evolution observed in other studies; rather, they suggest a hyperplastic nature. However, the capacity of hyper mucinous raised lesions for neoplastic evolution should be ruled out with more extensive prospective studies to identify functional defects that could explain the hypothesized neoplastic potential.
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Introduction: Anal squamous cell carcinoma (ASC) is a rare gastrointestinal malignancy showing an increased incidence over the past decades. YKL-40 is an immune modulator and pro-angiogenetic factor that showed a promising prognostic and predictive potential in several malignancies, but limited data are available for ASC. This study aims to provide an extensive evaluation of the prognostic and predictive role of YKL-40 in a multicenter cohort of ASC patients. Methods: We retrospectively retrieved 72 consecutive cases of ASC diagnosed between February 2011 and March 2021. Both serum and tissue protein expression of YKL-40 were assessed, the latter in ASC tumor cells and peritumor immune cells. Results: Increased YKL-40 serum levels at the time of diagnosis were associated with older age (p = 0.035), presence of cardiovascular/metabolic comorbidities (p = 0.007), and death for any cause (p = 0.011). In addition, high serum levels of YKL-40 were associated with a poor prognosis (HR: 2.82, 95% CI: 1.01-7.84; p = 0.047). Protein expression of YKL-40 in ASC tumor cells was significantly associated with low tumor grade (p = 0.031), while the increased expression in peritumor immune cells was associated with a worse response of patients to chemoradiotherapy (p = 0.007). However, YKL-40 protein expression in ASC tumor cells or peritumor immune cells did not significantly impact patient overall survival. Discussion: In conclusion, YKL-40 resulted a relevant prognostic (serum level) and predictive (tissue protein expression in peritumor immune cells) biomarker and can considerably improve ASC patient clinical management.
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(1) Background: when the pathologist faces histologic slides from colonoscopies in daily practice, given the large number of entities and etiologies under inflammatory bowel conditions, in-depth definition of the histological spectrum and the recommendations of current guidelines are often not enough to conclusively define a diagnostic framework. Histological patterns should be organized hierarchically in flowcharts that consider the correlation with clinical data. We conducted an online survey asking a group of gastroenteropathologists to apply a pattern classification based on the most significant lesions in colitis differential diagnosis: crypt distortion and activity. (2) Methods: digital slides from 20 endoscopy samples were analyzed by twenty pathologists and classified according to the occurrence of crypt distortion (nondestructive-destructive colitis) and subsequently to the evidence of activity (ND1-2-3, D1-2). (3) Results: in 8 out of 20 (40%) cases, the participants reached a full agreement regarding the evaluation of crypt distortion (5 cases: nondestructive colitis; 3 cases: destructive colitis). The calculated agreement was k = 0.432. In the second-level quiz (ND1-2-3 and D1-2), full agreement between participants was achieved for 7 of the 28 (25%) possible classifications, with k = 0.229. (4) Conclusions: The findings from this survey are indicative of an unexpectedly low consensus, even among dedicated pathologists, about the recognition of histological changes that are commonly considered critical lesions in the histologic identification of bowel non-neoplastic diseases. In our opinion, these divergences imply a significant risk of misdiagnosis of bowel inflammatory conditions, hampering the usefulness of histological assessment.
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Teduglutide is a glucagon-like peptide-2 (GLP-2) analog employed in patients with short bowel syndrome (SBS) to reduce the need of parenteral nutrition in these patients, by virtue of its effects on enteric function. The experimental studies reported that the stimulating action of GLP-2 on epithelial turnover implies the potential development of dysplastic and neoplastic lesion. However, the clinical trials could not detect preneoplastic lesions on histologic material, and in a recent pilot study the occurrence of polyps was similar before and after treatment and included only low-grade dysplastic lesions. Another clue in GLP-2 function in stimulating mucosal restore is its enhancement through cooperation with epidermal growth factor (EGF). In this study, we analyzed gastroscopy and colonoscopy samplings from a child successfully weaned off parenteral nutrition with teduglutide. Villous and crypt structure was regular both in duodenal and in colonic samplings; in properly oriented villi, villus/crypt ratio was regular. The absorptive epithelium demonstrated a regular morphology. No atypia was detected in enterocytes, along epithelial structures. At the ultrastructural analysis, only a few enterocytes with vacuolized cytoplasm were observed. An S-phase marker Ki67 stained nuclei in the transitional amplifying zone, while nuclei stained by the cell cycle regulatory proteins p21 and p27 were placed in the differentiated epithelium of the duodenal villi and colonic crypts, as in the control cases. The counts of enterocytes immunostained with the same antisera, evaluated with image analysis software, were in the range of control cases. The ratio of the number of epidermal growth factor receptor (EGFR) signals/the number of centromere probe of chromosome 7 (CEP7) signals was less than 2. The findings available from this single patient are consistent with good preservation of functional capability of intestinal epithelium after treatment with GLP-2, given the histologic and ultrastructural features of enterocytes. In addition, the findings from cell cycle regulatory proteins immunolocalization and quantitative analysis show that cell renewal machinery in our case is comparable to control cases. The gene of the receptor EGFR is regularly expressed in enteric epithelium of our case. Morphologic and functional data from our patient improve evidence in favor of the safety of GLP-2 employ in SBS.
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The management of endoscopically resected pT1 colorectal cancer (CRC) relies on nodal metastasis risk estimation based on the assessment of specific histopathological features. Avoiding the overtreatment of metastasis-free patients represents a crucial unmet clinical need. By analyzing a consecutive series of 207 pT1 CRCs treated with colectomy and lymphadenectomy, this study aimed to develop a novel clinicopathological score to improve pT1 CRC metastasis prediction. First, we established the clinicopathological profile of metastatic cases: lymphovascular invasion (OR: 23.8; CI: 5.12-110.9) and high-grade tumor budding (OR: 5.21; CI: 1.60-16.8) correlated with an increased risk of nodal metastasis, while age at diagnosis >65 years (OR: 0.26; CI: 0.09-0.71) and high tumor-infiltrating lymphocytes (OR: 0.19; CI: 0.06-0.59) showed a protective effect. Combining these features, we built a five-tier risk score that, applied to our series, identified cases with a higher risk (score ≥ 2) of nodal metastasis (OR: 7.7; CI: 2.4-24.4). Notably, a score of 0 was only assigned to cases with no metastases (13/13 cases) and all the score 4 samples (2/2 cases) showed nodal metastases. In conclusion, we developed an effectively combined score to assess pT1 CRC nodal metastasis risk. We believe that its adoption within a multidisciplinary pT1 unit could improve patients' clinical management and limit surgical overtreatment.
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The COVID-19 pandemic has caused a worldwide significant drop of admissions to the emergency department (ED). The aim of the study was to retrospectively investigate the pandemic impact on ED admissions, management, and severity of three abdominal emergencies (appendicitis, diverticulitis, and cholecystitis) during the COVID-19 pandemic using 2017-2019 data as a control. The difference in clinical and pathological disease severity was the primary outcome measure while differences in (i) ED admissions, (ii) triage urgency codes, and (iii) surgical rates were the second ones. Overall, ED admissions for the selected conditions decreased by 34.9% during the pandemic (control: 996, 2020: 648) and lower triage urgency codes were assigned for cholecystitis (control: 170/556, 2020: 66/356, p < 0.001) and appendicitis (control: 40/178, 2020: 21/157, p = 0.031). Less surgical procedures were performed in 2020 (control: 447, 2020: 309), but the surgical rate was stable (47.7% in 2020 vs. 44.8% in 2017-2019). Considering the clinical and pathological assessments, a higher percentage of severe cases was observed in the four pandemic peak months of 2020 (control: 98/192, 2020: 87/109; p < 0.001 and control: 105/192, 2020: 87/109; p < 0.001). For the first time in this study, pathological findings objectively demonstrated an increased disease severity of the analyzed conditions during the early COVID-19 pandemic.
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Pancreatic neuroendocrine tumors (PanNETs) are rare neoplasms that include even rarer variants that may pose different diagnostic problems, especially in fine needle aspiration cytology (FNAC). We describe the diagnostic clues of the amyloid-rich variant of PanNETs in endoscopic ultrasound (EUS)-guided fine needle aspiration cytology (EUS-FNAC). Three cases of PanNETs with an amyloid-rich stromal component were retrieved and retrospectively reviewed. For every case, the pancreatic lesion was investigated by a EUS-FNAC procedure. The final diagnosis was supported by immunocytochemistry and Congo red staining. All cases had similar EUS-FNAC features: neoplastic cells were entrapped in an eosinophilic, homogeneous dense and amorphous matrix. The neuroendocrine nature was confirmed by immunoexpression of synaptophysin and chromogranin A, while the amorphous stroma was characterized as amyloid based on positive Congo red staining. Regarding the hormonal profile, no insulin or proinsulin reactivity was observed, but all cases were diffusely positive for amylin. The diagnosis of uncommon variants of PanNETs, such as the amyloid-rich, is challenging especially in EUS-FNAC procedures because of a unique and misleading morphology, potentially mimicking fibrotic conditions and amyloid deposition within systemic amyloidosis. In cytology specimens, the presence of amorphous material requires amyloid deposition to be considered in the differential diagnosis of pancreatic neoplasms with neuroendocrine phenotype.
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Amiloide/metabolismo , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Ectopic adrenal rests are a rare condition which can be found in various sites, generally in the retroperitoneum or pelvis along the path of gonadal descent. Their real prevalence is unknown. Males are more commonly affected, at least in the pediatric age. Adrenal rests are usually clinically silent and incidentally found in surgical samples, mostly in the pediatric population, and rarely in adults. With the aim of increasing knowledge and estimating the prevalence of ectopic adrenocortical tissue in the adult population, 44 adrenal rests in the urogenital tract of 40 adults are described. These represent approximately 0.07% of the total number of urogenital and gynecological surgeries performed in the 22 considered years. Adrenal rests were identified in the spermatic cord (10 males) and in paraovarian, parasalpingeal, or infundibulopelvic ligament locations (30 females). All but one was incidental findings. One case regarded an adrenocortical carcinoma arisen in adrenal rests. A literature review of adrenal ectopia in the urogenital tract of adults identified 57 reported cases from 53 patients, with similar clinicopathological features as those of our series, with the exception of a lower incidence of parasalpingeal locations. Despite their limited clinical implications, awareness of ectopic adrenal rests is essential also in adults for at least two reasons: (a) to correctly identify sources of adrenocortical hormone production in case of adrenal insufficiency or hormonal imbalance and (b) to avoid misinterpretations in the diagnostic workup of renal cell carcinoma, adrenocortical tumors, and rare gonadal neoplasms, including Sertoli/Leydig cell tumors.
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Glândulas Suprarrenais , Coristoma/patologia , Doenças Urogenitais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Coristoma/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Doenças Urogenitais/epidemiologiaRESUMO
Spread Through Air Spaces (STAS) is a form of invasion characterized by neoplastic cell dissemination in the lung parenchyma surrounding the outer edge of the tumor. Its possible artifactual origin is widely debated in the literature. The aim of this study is to investigate the potential impact of gross sampling procedures in causing STAS. A prospective series of 51 surgical lung specimens was collected (35 adenocarcinomas, 68.6%; 13 squamous cell carcinomas, 25.5%; 2 large-cell neuroendocrine carcinomas, 3.9%; 1 atypical carcinoid, 2%). The fresh tissue was sectioned with a new and clean blade for each cut, to obtain a tissue slice comprising the upper lung parenchyma, the tumor, and the lower parenchyma. This slice was cut in half and separately processed. The same procedure was repeated in the residual (specular) specimen after formalin fixation. STAS was identified in 33/51 (64.7%) cases, the predominant pattern being cluster formation (29 cases, 87.9%), the remaining 4 cases having single-cell invasion. Comparing STAS detection in upper and lower lung parenchyma areas (ie, before and after the blade crossed the tumor), no significant preferential STAS distribution was observed, indeed being almost overlapping (60.6% and 63.6% for fresh and 61.3% and 65.6% for fixed tissues, respectively). There was no difference between STAS occurrence in freshly cut and fixed corresponding samples. These findings indicate that STAS is not a pathologist-related artifactual event because of knife transportation of tumor cells during gross specimen handling and support the notion that it is a phenomenon preexisting to surgical tissue processing.
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Artefatos , Neoplasias Pulmonares/patologia , Manejo de Espécimes/efeitos adversos , Humanos , Invasividade Neoplásica/patologiaRESUMO
PURPOSE: Several ultrasound (US) risk stratification systems (US-RSSs) have been proposed to stratify the risk of malignancy (ROM) of thyroid nodules. This risk might be overestimated due to selection bias and comparison with the cytological report alone. Our study aimed to compare ROM and diagnostic performance of three guidelines (ATA, AACE/ACE/AME, EUTIRADS) and evaluate the changes in unnecessary biopsy according to the nodule size cutoff for biopsy, using histology as gold standard. METHODS: This retrospective observational study included 146 consecutive patients who underwent surgery after US and cytological characterization. We analyzed the effectiveness and accuracy of three US-RSSs. RESULTS: 46.6% of nodules were diagnosed as malignant. Applying US-RSS, the percentage of nodules that should have been analyzed by biopsy was 84.25% with ATA, 69.86% with EUTIRADS and 64.38% with AACE/ACE/AME systems. The ROM was 94.9%, 86.0%, 87.0% for high-risk category, 36.4%, 32.0%, 35.4% for intermediate-risk category and 22.9%, 0.0%, 22.9% for low-risk category by ATA, AACE/ACE/AME and EUTIRADS systems, respectively. EUTIRADS and AACE/ACE/AME systems were more accurate in differentiating malignant from benign cases. ATA score was the more sensitive US-RSS to identify malignant tumors within the high-risk category. About the unnecessary biopsies, in the intermediate-risk category, the application of the size criterion helps to increase specificity in all systems. CONCLUSIONS: The US categorization of low and high-risk thyroid nodules using current US-RSSs helps alone to determine the optimal treatment option. Nodule size remains relevant to recommend biopsy for the intermediate-risk category.