In the context of neoplasia, acellular mucin in lower gastrointestinal (GI) tract implies occult mucin-producing tumor and warrants additional workup. The clinical significance of acellular mucin in benign conditions remains unclear.

Lower GI tract surgical specimens with acellular mucin without documented neoplastic conditions (colonic diverticulitis (n = 16), appendicitis (n = 14), and others (n = 8)) were retrieved. Low grade appendiceal mucinous neoplasm (LAMN) (n = 24) and diverticulitis without acellular mucin (n = 28) were used as controls for appendicitis and diverticulitis cases, respectively. Clinical data, histological findings, and additional workups performed due to acellular mucin were collected.

Patients with appendicitis with acellular mucin frequently presented with signs and symptoms of acute appendicitis (p = 0.016) compared to LAMN. 71 % were interval appendectomy, and 57 % had diverticula. In colonic diverticulitis cohort, no differences were found in terms of the duration of symptoms, age, gender and the degree of inflammation between the groups with and without acellular mucin. Seven of 8 patients with other conditions with acellular mucin had a history of abdominal surgery or fistula. Additional workup included levels (n = 7), consults (n = 11), and stains (n = 4).

Acellular mucin can be seen in a variety of benign conditions but this phenomenon is probably under-recognized and leads to additional investigations. Acellular mucin is likely translocated from the lumen through diverticulum or mural defect. Considering clinical context is crucial in providing accurate diagnosis while preserving laboratory resources.

In the digestive system, intraoperative frozen sections are commonly requested to assess surgical margins, obtain diagnostic material, and evaluate incidental lesions. Frozen section results may alter surgical planning or lead to the discontinuation of the procedure. As a practicing pathologist, understanding the indication for frozen section and its impact on patient management would improve communication with surgeons. Likewise, understanding what to look for and focus on, what to relay to the requester and common diagnostic pitfalls would improve the quality of service one provides and patients' outcome. Herein we provide an overview of common frozen sections encountered during variable abdominal procedures to include pancreaticoduodenectomy, gastrectomy, appendectomy, colorectal resection and Hirschsprung pull-through along with ample microscopic images.

We explored the use of MRI T2-weighted imaging (T2WI) radiomics to help distinguish acellular mucin from cellular mucin (residual tumor) to inform patient management.

This retrospective, multi-institutional study included consecutive patients with rectal adenocarcinoma containing mucin on restaging MRI from March 2012-January 2020. Radiologists segmented 3-mm-thick T2WI. Data were split into training (n = 122), validation (n = 40), and test (n = 42) sets. Sensitivity, specificity, PPV, NPV, and AUC of the developed radiomic models were investigated on the test set. Histopathology was the reference standard. Two radiologists independently reviewed 42 patients using a unique five-point Likert scale for the probability of cellular mucin. DeLong-Delong or McNemar's test was used to compare the AUC and diagnostic performance, respectively, of the radiomics model to that of the human readers.

Of 204 patients (mean age, 56.6 ± 13.3 years; 129 men and 75 women), 39/204 (19 %) had acellular mucin whereas 165/204 (81 %) had cellular mucin. The radiomics model demonstrated a sensitivity of 90 % (27/30, 95 % CI: 74-97 %), specificity of 83 % (10/12, 95 % CI: 55-95 %), PPV of 93 % (27/29, 95 % CI: 78-98 %), NPV of 77 % (10/13, 95 % CI: 50-92 %), and AUC of 0.84 (95 % CI: 0.65-0.99), whereas the human readers showed inferior sensitivities of 47 % (14/30) (95 % CI: 28-66 %) and 50 % (15/30) (95 % CI: 31-69 %) and AUCs of 0.58 (95 % CI: 0.41-0.74) (DeLong's p = 0.06 [95 % CI: -0.55, 0.01]) and 0.73 (95 % CI: 0.57-0.88) (DeLong's p = 0.43 [95 % CI: -0.39, 0.16]).

The developed MRI radiomics model predicts cellular mucin post neoadjuvant chemoradiation with higher sensitivity than human readers.

Rectal cancer is one of the most frequent malignancies worldwide. The most common histological type is adenocarcinoma, followed by mucinous adenocarcinoma. The outcome is less favorable for the mucinous type, yet the treatment course is the same. The aim of this systematic literature review is to assess existing information in order to improve survival in rectal mucinous adenocarcinoma (RMA) and establish a starting point for future research. A systematic search of PubMed, Google Scholar, and Web of Science online libraries was performed in October 2024, evaluating studies regarding clinicopathological and genetic features in connection with targeted treatment and survival outcomes in RMA, using the terms "rectal cancer", "rectum", "mucinous adenocarcinoma", or a combination of the terms. We selected 23 studies, 10 of them regarding the diagnostic implications and 13 discussing the treatment strategies and prognosis of this histological subtype. There were six studies addressing the imaging aspects, highlighting the distinct features of mucinous histology in MRI. The molecular specifics were detailed in four studies, outlining the molecular footprint. The prognosis and treatment course were addressed in 12 studies. The inflammation index prognosis, complete response to neoadjuvant chemotherapy, and surgical aspects were addressed individually in each study. We encapsulated the molecular and clinicopathological characteristics of RMA, as well as diagnostic and treatment approaches, to establish a baseline of references for the benefit of daily practice and further research.

Colorectal cancer (CRC) is a neoplasm with a high prevalence worldwide, with a multimodal treatment that includes a combination of chemotherapy, radiotherapy, and surgery in locally advanced stages with acceptable pathological complete response (pCR) rates, this has improved with the introduction of total neoadjuvant therapy (TNT) reaching pCR rates up to 37% in compare with classic neoadjuvant treatment (NAT) where pCR rates of around 20-25% are achieved. However, the patient population that benefits most from this therapy has not been determined, and there is a lack of biomarkers that can predict the course of the disease. Multiple biomarkers have been studied, ranging from hematological and molecular markers by imaging technique and combinations of them, with contradictory results that prevent their use in routine clinical practice. In this review, we evaluate the most robust prognostic biomarkers to be used in clinical practice, highlighting their advantages and disadvantages and emphasizing biomarker combinations and their predictive value.

The present study aimed to compare the effectiveness of two abbreviated magnetic resonance imaging (MRI) protocols in assessing the response to neoadjuvant chemoradiotherapy (CRT) in patients with rectal cancer. Data from the examinations of 62 patients with rectal cancer who underwent neoadjuvant CRT and standard contrast-enhanced rectal MRI were retrospectively evaluated. Standard contrast-enhanced T2-weighted imaging (T2-WI), post-contrast T1-weighted imaging (T1-WI) and diffusion-weighted imaging (DWI) MRI, as well as two abbreviated protocols derived from these images, namely protocol AB1 (T2-WI and DWI) and protocol AB2 (post-contrast fat-suppressed (FS) T1-WI and DWI), were assessed. Measurements of lesion length and width, lymph node short-axis length, tumor staging, circumferential resection margin (CRM), presence of extramural venous invasion (EMVI), luminal mucin accumulation (MAIN), mucinous response, mesorectal fascia (MRF) involvement, and MRI-based tumor regression grade (mrTRG) were obtained. The reliability and compatibility of the AB1 and AB2 protocols in the evaluation of tumor response were analyzed. The imaging performed according to the AB1 and AB2 protocols revealed significant decreases in lesion length, width and lymph node size after CRT. These protocols also showed reductions in lymph node positivity, CRM, MRF, EMVI.Furthermore, both protocols were found to be reliable in determining lesion length and width. Additionally, compliance was observed between the protocols in determining lymph node size and positivity, CRM involvement, and EMVI after CRT. In conclusion, the use of abbreviated MRI protocols, specifically T2-WI with DWI sequences or post-contrast FS T1-WI with DWI sequences, is effective for evaluating tumor response in patients with rectal cancer following neoadjuvant CRT. The AB protocols examined in this study yielded similar results in terms of lesion length and width, lymph node positivity, CRM involvement, EMVI, MAIN, and MRF involvement.

Neoadjuvant therapy leads to a clinical complete response in a considerable proportion of patients with locally advanced rectal cancer, allowing for possible nonoperative management. The presence of mucin on magnetic resonance imaging (MRI) after neoadjuvant therapy leads to uncertainty about residual disease and appropriateness of a watch-and-wait strategy in patients with no evidence of disease on proctoscopy (endoscopic clinical complete response).

MRI reports for locally advanced rectal cancer patients seen between July 2016 and January 2020 at Memorial Sloan Kettering Cancer Center were queried for presence of mucin in the tumor bed on MRI following neoadjuvant therapy. Clinicodemographic, pathologic, and outcome data were compiled and analyzed.

Of 71 patients with mucin on posttreatment MRI, 20 had a clinical complete response, and 51 had abnormalities on endoscopy and/or physical exam. One patient with a clinical complete response opted out of watch-and-wait; thus, 19 (27%) patients entered watch-and-wait, and 52 (73%) patients were planned for surgery (non-watch-and-wait). Of the 19 watch-and-wait patients, 15 (79%) have had no local regrowth with median follow-up of 50 months (range = 29-76 months), while 4 (21%) experienced regrowth between 9 and 29 months after neoadjuvant therapy. Of the 52 patients who were planned to have surgery (non-watch-and-wait), 49 underwent resection while 3 developed metastatic disease that precluded curative-intent surgery. Of the 49 patients who underwent surgery, 5 (10%) had a pathologic complete response (including the patient with an endoscopic clinical complete response).

The presence of mucin after neoadjuvant therapy for locally advanced rectal cancer does not preclude watch-and-wait management in otherwise appropriate candidates who achieve an endoscopic clinical complete response.

In around 30% of patients, non-small cell lung cancer is diagnosed at an advanced but resectable stage. Adding systemic therapy has shown clear benefit over surgery alone in locally advanced disease, and currently, chemo-immunotherapy in the adjuvant or neoadjuvant setting is the new standard for patients without targetable mutations. One major advantage of the neoadjuvant approach is the possibility of an immediate evaluation of the treatment effect, highlighting the role of pathology as an important contributor at the forefront of clinical decision-making and research. This review provides a summary and an update on current guidelines for histological evaluation of treatment effect after neoadjuvant therapy, also known as regression grading, and discusses newer data focusing on areas of evolving questions and controversies, such as the gross examination of the tumor and tumor bed, weighted versus unweighted evaluation approaches, discussion of histologic tumor type-specific cut-offs for major pathologic response, assessment of lymph nodes and regression grading after immunotherapy and targeted therapy. As no data or recommendations exist on regression grading of multiple tumor nodules, a practical approach is recommended. Lastly, we will touch on additional tissue biomarkers and summarize recent advances in the ardently discussed field of using circulating tumor DNA for the evaluation of treatment response.

Purpose:  Magnetic resonance imaging (MRI) with the help of MRI-based tumor regression grade (mrTRG) score has been used as a tool to predict pathological tumor regression grade (pTRG) in patients of rectal cancer post-neoadjuvant chemoradiation. Our study aims to evaluate the ability of MRI in assessing treatment response comparing an objective mrTRG score and a subjective Likert score, with a focus on the ability to predict pathologic complete response (pCR). Methods:  Post-treatment MRI studies were retrospectively reviewed for 170 consecutive cases of histopathologically proven rectal cancer after receiving neoadjuvant chemoradiation and prior to surgery by two oncoradiologists blinded to the eventual postoperative histopathology findings. An objective (mrTRG) and a subjective Likert score were assigned to all the cases. Receiver operating characteristic curves were constructed to determine the ability of Likert scale and mrTRG to predict pCR, with postoperative histopathology being the gold standard. The optimal cutoff points on the scale of 1 to 5 were obtained for mrTRG and Likert scale with the greatest sum of sensitivity and specificity using the Youden Index. Results:  The most accurate cutoff point for the mrTRG to predict complete response was 2.5 (using Youden index), with a sensitivity of 69.2%, specificity of 69.6%, positive predictive value (PPV) of 85.6%, negative predictive value (NPV) of 46.4%, and accuracy of 69.3%. The most accurate cutoff for the Likert scale to predict complete response was 3.5, with a sensitivity of 47.5%, specificity of 89.1%, PPV of 91.9%, NPV of 39.4%, and accuracy of 59%. mrTRG had a lower cutoff and was more accurate in predicting pCR compared to Likert score. Conclusion:  An objective mrTRG was more accurate than a subjective Likert scale to predict complete response in our study.

BACKGROUND. Patients with nonmucinous rectal adenocarcinoma may develop mucinous changes after neoadjuvant chemoradiotherapy, which are described as mucinous degeneration. The finding's significance in earlier studies has varied. OBJECTIVE. The purpose of this study was to assess the frequency of mucinous degeneration on MRI after neoadjuvant therapy for rectal adenocarcinoma and to compare outcomes among patients with nonmucinous tumor, mucinous tumor, and mucinous degeneration on MRI. METHODS. This retrospective study included 201 patients (83 women, 118 men; mean age, 61.8 ± 2.2 [SD] years) with rectal adenocarcinoma who underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision from October 2011 to November 2015, underwent baseline and restaging rectal MRI examinations, and had at least 2 years of follow-up. Two radiologists independently evaluated MRI examinations for mucin content, which was defined as T2 hyperintensity in the tumor or tumor bed, and resolved differences by consensus. Patients were classified into three groups on the basis of mucin status: those with nonmucinous tumor (≤ 50% mucin content on baseline and restaging examinations), those with mucinous tumor (> 50% mucin content on baseline and restaging examinations), and those with mucinous degeneration (≤ 50% mucin content on baseline examination and > 50% content on restaging examination). The three groups were compared. RESULTS. Interreader agreement for mucin content, expressed as a kappa coefficient, was 0.893 on baseline MRI and 0.890 on restaging MRI. Of the 201 patients, 156 (77.6%) had nonmucinous tumor, 34 (16.9%) had mucinous tumor, and 11 (5.5%) had mucinous degeneration. Mucin status was not significantly associated with complete pathologic response (p = .41) or local or distant recurrence (both p > .05). The death rate during follow-up was not significantly different (p = .21) between patients with nonmucinous tumor (23.1%), those with mucinous tumor (29.4%), and those with mucinous degeneration (9.1%). In adjusted Cox regression analysis, with mucinous degeneration used as reference, the HR for the overall survival rate for the mucinous tumor group was 4.7 (95% CI, 0.6-38.3; p = .14), and that for the nonmucinous tumor group was 8.0 (95% CI, 0.9-59.9; p = .06). On histopathologic assessment, all 11 patients with mucinous degeneration showed acellular mucin, yet 10 of 11 patients showed viable tumor (i.e., in nonmucinous portions of the tumors). CONCLUSION. Mucinous degeneration on MRI is not significantly associated with pathologic complete response, recurrence, or survival. CLINICAL IMPACT. Mucinous degeneration on MRI is uncommon and should not be deemed an indicator of pathologic complete response.

Pancreatic neuroendocrine tumors (PanNETs) in familial tuberous sclerosis (TSC1 and TSC2 mutations) have been known and studied. However, little is known about PanNET patients harboring the very rare (less than 2%) sporadic TSC mutations. Some renal tumors have been shown to harbor sporadic TSC mutations, with a distinctive morphological correlate. We hereby describe this rather unusual molecular alteration in well-differentiated pancreatic neuroendocrine tumors (WD PanNETs) with a focus on their morphology and treatment outcomes. Six cases of WD PanNETs harboring sporadic TSC mutations were identified retrospectively. H&E slides and corresponding immunostains were reviewed for all cases. Clinical, molecular, and radiological information was obtained using the electronic medical records. Cohort consisted of 4 males and 2 females. Median age at diagnosis was 50 years (range 33-74 years). Origin of neoplasm was the pancreas and, in all but one, patient had liver metastasis by the time of presentation. Six out of six cases demonstrated a unique tumor morphology, with ample eosinophilic cytoplasm. Tumors were arranged in sheets and nests; prominent cystic change was noted in one case. Two cases were additionally biopsied post-treatment with capecitabine and temozolomide, and showed even more abundant oncocytic cytoplasm, eccentric nuclei, and a prominent cherry red nucleolus, and were arranged in a cluster of 3-4 cells, separated by stromal cells. Every patient had a different TSC2 variant with no cases of TSC1 mutations. Other common variants included MEN1 (4/6), DAXX (2/6), and TP53 (2/6). Per the WH0 2019 classification, tumors were graded as NET-G3 (n = 3) and NET-G2 (n = 3). Ki-67 s ranged from 7.2 to 60. All cases had retained MMR protein expression. The majority of patients (4/6) have expired. Although they received multiple treatments, a consistent pattern observed in patients was marked radiologic response to chemotherapy with capecitabine and temozolomide (offered in 5/6 patients) with duration of responses reaching 11 months in the majority of cases, with one patient showing near complete pathologic response of localized disease. TSC2 mutations may confer distinctive appearance in WD PanNETs, reminiscent of their effects in renal tumors. Although not entirely specific, this distinct morphological pattern with abundant eosinophilic cytoplasm in WD PanNETs could be reflective of an associated TSC mutation, with suggestions of significant therapeutic response to a specific cytotoxic chemotherapy.

For patients with locally advanced rectal cancer (LARC) with pathological complete response (pCR), the clinical significance of the distribution extent of acellular mucin pools (AMP) distribution remains unclear, so this study was conducted to address key unanswered questions. We performed a retrospective analysis of 317 patients with LARC with pCR after preoperative chemoradiotherapy and total mesorectal resection from January 2011 to June 2020. Based on AMP existence and the deepest tissue layer of distribution, patients were assigned new stages. The patient information was recorded, and the main outcome measures included 5-year disease-free survival (DFS) and 5-year overall survival (OS). A total of 83/317 (26.2%) patients exhibited AMP, and disease recurrence occurred in 46/317 (14.5%) patients. Over the 5-year median follow-up period, the patients with AMP showed 5-year DFS rates (75.9% vs. 88.9%, P =0.004) and 5-year OS rates (85.5% vs. 95.7%, P =0.002) statistically lower than those of patients without AMP. Disease recurrence was seen in 15/54 (27.8%) patients with AMP within the subserosa and/or the serosa, or adipose tissue. Univariate and multivariate analysis showed that the existence of AMP within the subserosa and/or the serosa, or adipose tissue was an independent risk factor for DFS [hazard ratio (HR): 2.344; 95% confidence interval (CI): 1.256-4.376; P =0.007] and OS [HR: 3.374; 95% CI: 1.438-7.917; P =0.005]. The new stages based on the deepest extent of AMP were related to worse DFS ( P =0.004) and OS ( P =0.003) rates among patients with pCR. In conclusion, the presence of AMP might reduce the prognosis of LARC patients with pCR after chemoradiotherapy, especially in patients with AMP in deeper tissue layers. Therefore, the influence of the deepest AMP extent might be worth considering in staging. Moreover, the revised staging of patients with pCR according to the deepest extent of AMP, which is unrelated to the clinical T stage, might facilitate postoperative management.

Approximately 15-30% of locally advanced rectal cancer (LARC) patients achieved pathological complete response (pCR) after neoadjuvant chemoradiotherapy (CRT) and total mesorectal excision, but the clinical significance of adjuvant chemotherapy (ACT) for pCR patients remains unclear.

To determine whether LARC pCR patients can benefit from the administration of ACT.

Single center retrospective study.

This study retrospectively included 280 LARC patients who achieved pCR after CRT and surgery from 2011 to 2019. The information of patients was recorded. Main outcome measures included 5-year disease-free survival (DFS) and 5-year overall survival. Subgroup analysis was conducted on whether pCR patients with acellular mucin pools received ACT or not.

A total of 74/280 (26.4%) patients were identified with acellular mucin pools. Disease recurrence occurred in 38/280 (13.6%) patients, and in the subgroup of patients with acellular mucin pools, 15/74 (20.3%) patients developed distant metastases. The existence of acellular mucin pools was associated with worse DFS (79.7% versus 88.8%, P = 0.037). Among pCR patients with acellular mucin pools, 9/25 (36.0%) of non-ACT patients occurred recurrence, and ACT was beneficial for improving DFS (hazard ratio: 0.245; 95% confidence interval: 0.084-0.719; P = 0.010).

The existence of acellular mucin pools may represent a sign of invasive tumor biology, which indicated a negative prognosis. ACT can improve the prognosis of patient with acellular mucin pools, so ACT should be considered for them.

In recent years, several key advances in the management of locally advanced rectal cancer have been made, including the implementation of total mesorectal excision as the standard surgical approach; use of neoadjuvant chemoradiotherapy in selected patients with a high risk of local recurrence, and finally, adoption of organ preservation strategies, through either local excision or nonoperative management in selected patients with clinical complete response following neoadjuvant chemoradiotherapy. This review aims to shed light on the role of rectal MRI in the assessment of treatment response after neoadjuvant therapy, which is especially important given the growing feasibility of nonoperative management. First, an overview of current neoadjuvant therapies and response assessment based on digital rectal examination, endoscopy, and MRI will be provided. Second, the use of a high-quality restaging rectal MRI protocol will be presented. Third, a step-by-step approach to assessing treatment response on restaging rectal MRI following neoadjuvant treatment will be outlined, acknowledging challenges faced by radiologists during MRI interpretation. Finally, research related to response assessment will be discussed. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 3.

A comprehensive histopathology report of colorectal carcinoma surgery is important in cancer staging and planning adjuvant treatment. Our aim was to review histopathology reports of operated specimens of colorectal carcinoma in our institution between 2013 and 2015 to assess different histological parameters, including lymph node yield, and to evaluate compliance to minimum data sets.

After approval by the institutional review board (IRB), we analyzed 1230 histopathology reports of colorectal carcinoma between 2013 and 2015. Various gross and microscopic findings (along with age, sex) were noted, for example, specimen type, tumor site, resection margins including circumferential resection margin (CRM), lymphovascular invasion, perineural invasion, pTNM stage, lymph node yield, etc.

Out of 1230 patients, 826 (67.15%) were men and 404 (32.85%) were women. The overall mean age was 52 (range: 18 - 90) years. There were 787 surgeries for rectal cancers. All reports commented on the type of specimen, tumor size (mean = 4.38 cm), proximal, and distal margins. Lymphovascular invasion (LVI) and the pT stage were mentioned in 98.06% and 99.84%, respectively. The overall mean lymph node yield was 18.38 (median = 15, range = 0-130 lymph nodes). A statistically significant difference in lymph node yield was detected between rectal and colonic cancer patients (14.79 and 27.26); post neoadjuvant therapy (NACT) cases, and NACT naive cases (13.51 and 25.11); and high tumor stage and low tumor stage disease (20.60 and 15.22). Not commenting on extramural vascular emboli, tumor budding, and CRM in non-rectal cancer cases were the lacunae.

Our compliance with minimal data sets is satisfactory. The overall mean lymph node yield was 18.38 (median = 15). Extramural vascular emboli, tumor budding need to be captured.

Lymph nodes with acellular mucin harvested from treated colorectal cancers (CRC) are staged as pN0. However, there is variability among pathologists while reporting the pN stage when acellular mucin is found within nodes of untreated CRCs. While the UICC guidelines suggest staging them as pN1, the AJCC and CAP do not offer any recommendations. In order to characterize their clinicopathologic features and outcome, we compared 16 untreated CRCs (study group; mean age: 68 years) harboring nodes with acellular mucin with 34 pN0 and 25 pN1 untreated CRC controls. All tumors were unifocal; 12 (75%) were right-sided lesions. Most cases (75%) showed one node with acellular mucin (range: 1-3). MMR-deficient tumors were significantly more common in the study group (83%) compared to pN0 (33%; p = 0.006) and pN1 controls (8%; p < 0.001). The overall survival of study group patients was closer to pN0 compared to pN1 controls; however, this difference was not statistically significant. In conclusion, untreated CRC that harbor acellular mucin within lymph nodes commonly present as right-sided, MMR-deficient tumors in older women that show a non-mucinous phenotype. While the limited number of cases precludes us from making any formal recommendations about staging, we suggest that the finding of acellular mucin in a node should prompt evaluation of deeper levels (with or without cytokeratin immunohistochemistry) and submission of all pericolonic fat for additional lymph node harvest. Whether acellular mucin in nodes of untreated CRCs is related to the indolent biology of the disease, a robust local immune response or MMR deficiency requires further investigation.

Whole-block imaging (WBI) using micro-computed tomography (micro-CT) allows the nondestructive reconstruction of a three-dimensional view of tissues, implying that WBI may be used for accurate pathological evaluation of patients with rectal cancer. HOWEVER, the clinical impact of this approach is unclear. We aimed to clarify the efficacy of WBI in the whole-mount specimens of locally advanced rectal cancer. A total of 237 whole-mount formalin-fixed paraffin-embedded blocks from 13 patients with rectal cancer who underwent surgical treatment were enrolled and scanned with micro-CT to generate three-dimensional images. WBI was evaluated following the conventional pathological review of the corresponding whole-slide imaging (WSI). WBI identified all tumor sites detected using WSI. Furthermore, WBI revealed one additional tumor site, which was not detected using WSI. Tumor resection margin was significantly closer to the soft-tissue edge when measured using WBI (7.7 mm vs. 6.6 mm, p < 0.01). Seventy-six percent of tumor deposits on WSI were changed according to the evidence of tumor interaction with the surrounding tissues confirmed using WBI. Furthermore, WBI revealed 25 additional lymph nodes, six of which were metastatic. The combination of conventional hematoxylin and eosin-stained imaging and WBI may contribute to an accurate pathological assessment.

Rectal cancer is a relatively common malignancy in the United States. Magnetic resonance imaging (MRI) of rectal cancer has evolved tremendously in recent years, and has become a key component of baseline staging and treatment planning. In addition to assessing the primary tumor and locoregional lymph nodes, rectal MRI can be used to help with risk stratification by identifying high-risk features such as extramural vascular invasion and can assess treatment response for patients receiving neoadjuvant therapy. As the practice of rectal MRI continues to expand further into academic centers and private practices, standard MRI protocols, and reporting are critical. In addition, it is imperative that the radiologists reading these cases work closely with surgeons, medical oncologists, radiation oncologists, and pathologists to ensure we are providing the best possible care to patients. This review aims to provide a broad overview of the role of MRI for rectal cancer.

Epstein-Barr virus positivity (EBV+) and microsatellite instability (MSI-high) are positive prognostic factors for survival in resectable gastric cancer (GC). However, benefit of perioperative treatment in patients with MSI-high tumors remains topic of discussion. Here, we present the clinicopathological outcomes of patients with EBV+, MSI-high, and EBV-/MSS GCs who received either surgery only or perioperative treatment.

EBV and MSI status were determined on tumor samples collected from 447 patients treated with surgery only in the D1/D2 trial, and from 451 patients treated perioperatively in the CRITICS trial. Results were correlated to histopathological response, morphological tumor characteristics, and survival.

In the D1/D2 trial, 5-year cancer-related survival was 65.2% in 47 patients with EBV+, 56.7% in 47 patients with MSI-high, and 47.6% in 353 patients with EBV-/MSS tumors. In the CRITICS trial, 5-year cancer-related survival was 69.8% in 25 patients with EBV+, 51.7% in 27 patients with MSI-high, and 38.6% in 402 patients with EBV-/MSS tumors. Interestingly, all three MSI-high tumors with moderate to complete histopathological response (3/27, 11.1%) had substantial mucinous differentiation. No EBV+ tumors had a mucinous phenotype. 115/402 (28.6%) of EBV-/MSS tumors had moderate to complete histopathological response, of which 23/115 (20.0%) had a mucinous phenotype.

In resectable GC, MSI-high had favorable outcome compared to EBV-/MSS, both in patients treated with surgery only, and in those treated with perioperative chemo(radio)therapy. Substantial histopathological response was restricted to mucinous MSI-high tumors. The mucinous phenotype might be a relevant parameter in future clinical trials for MSI-high patients.

Mucinous carcinoma is a histological subtype of rectal cancer and has been associated with a poor response to neoadjuvant chemoradiotherapy (CRT). The primary aim of this study was to analyse the response on MRI of mucinous locally advanced rectal cancer (LARC) after CRT compared to regular adenocarcinoma.

Patients with LARC (defined as cT4 and/or cN2), who underwent CRT followed by restaging MRI and surgery in two tertiary referral hospitals were retrospectively included in the study. Pre- and post-treatment MRI was reviewed by an experienced abdominal radiologist.

A total of 102 patients, of whom 29 were diagnosed with mucinous carcinoma, were included for analysis. At restaging MRI, adenocarcinoma patients demonstrated significantly less clinical involvement of the mesorectal fascia (37% vs. 62%, P = 0.003) while this was not demonstrated in mucinous carcinoma patients (86% vs. 97%, P = 0.16). Significant downstaging after CRT in adenocarcinoma patients (P = 0.01) was seen while, in mucinous carcinoma patients, no downstaging after CRT (P = 0.89) was seen. Pathology revealed significantly higher rates of an involved circumferential resection margin in mucinous carcinoma versus adenocarcinoma patients (27.6% vs. 1.4%; P < 0.001). After multivariate regression analysis, mucinous carcinoma remained an independent prognostic factor for local recurrence (hazard ratio 3.6; 95% CI 1.1-12.4), although no differences in overall or disease-free survival were observed.

Mucinous rectal carcinoma is associated with a poor clinical response at restaging MRI after CRT, leading to relatively higher rates of involved circumferential resection margins at pathology. In this cohort, mucinous carcinoma seems to be a prognostic factor for increased risk of local recurrence, without an effect on overall survival.

Assessing metastatic mesorectal nodal involvement is a challenge in rectal cancer, especially in the post chemoradiation setting. We aim to assess the accuracy of MRI for nodal restaging and the validity of SAR criteria (≥ 5 mm size being metastatic).

This was an IRB-approved retrospective study of 166 patients with locally advanced rectal cancers, operated after neoadjuvant treatment. Two dedicated oncoradiologists reviewed the 166 post-chemoradiation presurgical MRIs in consensus. Nodal size and morphology (shape, margins, and signal intensity) were noted. The most accurate cut-off for size for predicting positive pN status was determined using the Youden index.

MRI understaged 30/166 (18%) and overstaged 40/166 (24%) patients using the SAR criteria. The most accurate cut-off for node size was 5.5 mm, with a sensitivity of 75%, specificity of 60.2%, PPV of 40.7%, NPV of 86.9% (95% CI:78-92.5%), accuracy of 64.2%, and area under the curve (AUC) 0.657 (95% CI-0.524-0.79). Morphological characteristics were not significant to determine involvement, with positive nodes including 42% of round and 31% of oval nodes, 40% of heterogeneous and 45% of homogeneous nodes, and 31% irregularly marginated and 46% nodes with regular margins being positive on pathology. MRI was accurate in predicting pathology for mucinous nodes in 9/29 (31%) cases. Seven cases which were yN2 on MRI and yN0 on pathology demonstrated mucinous changes on MRI and had acellular mucin on histopathology.

MRI has good negative predictive value, poor positive predictive value and moderate accuracy in nodal restaging. The cut-off of 5.5 mm demonstrated in our study is close to the SAR cut-off of 5 mm in the post-treatment setting. MRI accuracy is lower in patients with mucinous nodes.

To provide a practical overview regarding the state-of-the-art of the magnetic resonance imaging (MRI) protocol for rectal cancer imaging and interpretation during primary staging and restaging after neoadjuvant chemoradiation therapy (CRT), pointing out technical skills and findings that radiologists should consider for their reports during everyday clinical activity.

Both 1.5T and 3.0T scanners can be used for rectal cancer evaluation, using pelvic phased array external coils. The standard MR protocol includes T2-weighted imaging of the pelvis, high-resolution T2-weighted sequences focused on the tumor and diffusion-weighted imaging (DWI). The mnemonic DISTANCE is helpful for the interpretation of MR images: DIS, for distance from the inferior part of the tumor to the anorectal-junction; T, for T staging; A, for anal sphincter complex status; N, for nodal staging; C, for circumferential resection margin status; and E, for extramural venous invasion.

Primary staging with MRI is a cornerstone in the preoperative workup of patients with rectal cancer, because it provides clue information for decisions on the administration of CRT and surgical treatment. Restaging after CRT is crucial for treatment planning, and findings on post-CRT MRI correlate with the patient's prognosis and survival. It may be useful to remember the mnemonic word "DISTANCE" to check and describe all the relevant MRI findings necessary for an accurate radiological definition of tumor stage and response to CRT.

"DISTANCE" assessment for rectal cancer staging and treatment response estimation after CRT may be helpful as a checklist for a structured reporting.

To date, the prognostic significance of acellular mucin pools in tumors from patients with locally advanced rectal cancer (LARC) undergoing preoperative chemoradiotherapy (CRT) and subsequently obtaining pathological complete response (pCR) has not been well determined. Our current study aimed to explore the prognostic impact on these patients of acellular mucin pools.

We collected clinical data from 117 consecutive LARC patients who achieved pCR after preoperative CRT and then underwent radical resection. Two groups of patients were generated, according to the presence or absence of acellular mucin pools. The 5-year disease-free survival (DFS) and overall survival (OS) rates were compared between the two groups of patients.

A total of 27 (23.1%) patients presented with acellular mucin pools. At a median follow-up period of 64 months, patients with acellular mucin pool showed a 5-year DFS rate (96.3% versus 83.7%, p = 0.110) and 5-year OS rate (100% versus 87.5%, p = 0.054) statistically similar to those of patients without acellular mucin pools. In univariable and multivariable Cox regression analyses, the presence of acellular mucin pools was not determined as an independent risk factor for DFS [hazard ratio (HR): 0.222; 95% confidence interval (CI): 0.029-1.864; p = 0.145] or OS (HR: 0.033; 95% CI: 0.000-9.620; p = 0.238).

Acellular mucin pools had no significant prognostic impact on LARC patients showing pCR after preoperative CRT.

Peritoneal surface oncology has emerged as a subspecialty of surgical oncology, with the growing popularity of surgical treatment of peritoneal metastases comprising of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Pathological evaluation plays a key role in multidisciplinary management but there are still many areas where there are no guidelines or consensus on reporting. Some tumors presenting to a peritoneal surface oncology unit are rare and pathologists my not be familiar with diagnosing and classifying those. In this manuscript, we have reviewed the evidence regarding various aspects of histopathological evaluation of peritoneal tumors. It includes establishing a diagnosis, appropriate classification and staging of common and rare tumors and evaluation of pathological response to chemotherapy. In many instances, the information captured is of prognostic value alone with no direct therapeutic implications. But proper capturing of such information is vital for generating evidence that will guide future treatment trends and research. There are no guidelines/data set for reporting cytoreductive surgery specimens. Based on the authors' experience, a format for handling/grossing and synoptic reporting of these specimens is provided.

Challenges exist with standardized colorectal cancer reporting despite adoption of the American Joint Committee on Cancer-Staging Manual 8th edition. We performed this study to gauge current practice patterns among a diverse group of surgical pathologists. A web-based questionnaire depicting problematic issues and images related to colorectal carcinoma staging was circulated among 118 surgical pathologists and their responses were correlated with their geographic location (North America vs. Europe vs. others), nature of practice (academic vs. community), the sign-out model (gastrointestinal subspecialty vs. general surgical pathology), and years of professional experience. We found that a substantial number of practicing pathologists ignore recommended-staging criteria in specific settings, particularly with respect to assessment of advanced T stage. Tumors that communicated with the serosa through inflammatory foci were staged as pT3 (49%) or pT4a (51%) by nearly equal numbers of pathologists regardless of level of experience, the sign-out model, or geographic location. Only 65% assigned T stage and margin status based on extent of viable tumor in the neoadjuvant setting. One-third of pathologists, particularly those in Europe (p = 0.015), classified acellular mucin deposits as N1 disease when detected in treatment-naive cases. Nearly 50% of pathologists classified isolated tumor cells (i.e., deposits <0.2 mm) in lymph nodes as metastatic disease (i.e., pN1, p = 0.02). Our results suggest that pathologists ignore recommendations that are based on insufficient data and apply individualized criteria when faced with situations that are not addressed in the American Joint Committee on Cancer Staging Manual 8th edition. These variations in practice limit the ability to compare outcome data across different institutions and draw attention to areas that require further study.

An increasing number of patients with pancreatic ductal adenocarcinoma (PDAC) have undergone resection after neoadjuvant therapy (NAT). We have reported Area of Residual Tumor (ART) as a useful pathological assessment method to predict patient outcomes after post NAT resection in various cancer types. The aim of this study was to assess the prognostic performance of ART in PDAC resected after NAT. Sixty-three patients with PDAC after post NAT resection were analyzed. The viable residual tumor area was outlined and the measurement of ART was performed using morphometric software. The results were compared with those of the College of American Pathologist (CAP) regression grading. Of 63 cases, 39 (62%) patients received chemoradiation therapy and 24 (38%) received chemotherapy only. The median value of ART was 163 mm2. Large ART with 220 mm2 as the cut-off was significantly associated with lymphatic invasion, vascular invasion and perineural invasion, while CAP regression grading was not associated with any clinicopathological features. By multivariate analysis, large ART (≥220 mm2) was an independent predictor of shorter relapse free survival. Together with our previous reports, an ART-based pathological assessment may become a useful method to predict patient outcomes after post NAT resection across various cancer types.

Rectal adenocarcinoma with mucinous components is an uncommon type of rectal cancer with two distinct histologic subtypes: mucinous adenocarcinoma and signet-ring cell carcinoma. Mucin can also be identified as pattern of response after neoadjuvant treatment. On imaging modalities, mucin typically demonstrates high signal intensity on T2-weighted images, low attenuation on computed tomography, and may be negative on 18-fluorodeoxyglucose positron emission tomography. After neoadjuvant CRT, cellular and acellular mucin share similar imaging features, and differentiating them is currently the main challenge faced by radiologists. Radiologists should be aware of pros, cons, and limitations of each imaging modality in the primary staging and restaging to avoid misinterpretation of the radiological findings.

Standardized terminology is critical to providing consistent reports to referring clinicians. This lexicon aims to provide a reference for terminology frequently used in rectal cancer and reflects the consensus of the Society of Abdominal Radiology Disease Focused Panel in Rectal cancer. This lexicon divided the terms into the following categories: primary tumor staging, nodal staging, treatment response, anal canal anatomy, general anatomy, and treatments.

Rectal adenocarcinoma with mucinous components is an uncommon type of rectal cancer with two distinct histologic subtypes: mucinous adenocarcinoma and signet-ring cell carcinoma. Mucin can also be identified as pattern of response after neoadjuvant treatment. On imaging modalities, mucin typically demonstrates high signal intensity on T2-weighted images, low attenuation on computed tomography, and may be negative on 18-fluorodeoxyglucose positron emission tomography. After neoadjuvant CRT, cellular and acellular mucin share similar imaging features, and differentiating them is currently the main challenge faced by radiologists. Radiologists should be aware of pros, cons, and limitations of each imaging modality in the primary staging and restaging to avoid misinterpretation of the radiological findings.

Neoadjuvant chemoradiotherapy (CRT) is the standard of care for locally advanced rectal cancer. Morphologic changes such as fibrosis, inflammatory infiltrates, and the formation of extracellular mucin pools can be identified in the resection specimen after neoadjuvant CRT. The association of mucin pool formation with clinicopathologic variables and outcomes is unclear. The aim of this study was to meta-analyze all available evidence with regard to mucin pool formation and clinicopathologic outcomes following neoadjuvant CRT for rectal cancer. A comprehensive search for published studies analyzing outcomes between patients who formed mucin pools and patients who did not following neoadjuvant CRT for rectal cancer was performed. A random-effects model was used to combine the data. This study adhered to the recommendations of the MOOSE (Meta-analyses of Observational Studies in Epidemiology) guidelines. Data from 11 studies describing 1947 patients were included. Mucin pool formation was not associated with sex, T stage, N stage, tumor regression, pathologic complete response rate, lymphovascular invasion, perineural invasion, differentiation, margin status, local or distant recurrence, and disease-free or overall survival. Mucin pool formation is not associated with tumor response or downstaging; furthermore, on the basis of these data, it is not associated with local or systemic recurrence rate or survival.

Positive resection margins predict poor prognosis in rectal cancer (RC). Literature on the impact of acellular mucin (ACM) in circumferential resection margin (CRM) or distal resection margin (DRM) of proctectomy specimens on RC recurrence and outcomes is lacking. The retrospective study was conducted to determine the oncological outcomes of the RC patients with ACM in or within 1 mm of margins of the rectal resection specimens. Histopathology reports of RC resection specimens dated from June 2013 till May 2016 were reviewed to identify cases with ACM in CRM (n = 10) and DRM (n = 2). Relevant details of these patients were gathered from the electronic medical record. Pattern of recurrence was studied. In cases with only ACM in CRM (n = 10), disease (primary tumor or nodes) was radiologically reaching the mesorectal fascia except two, who had extra mesorectal nodes. Median distance of tumor from anal verge was 2 cm. All patient received neoadjuvant therapy: four patients received chemoradiotherapy (NACTRT), one received short-course radiotherapy, and five received NACTRT followed by neoadjuvant chemotherapy. Abdominoperineal resection, intersphincteric resection and total pelvic exenteration were done for six, three, and one patient, respectively. In two additional cases of anterior resection with ACM in DRM, one underwent upfront resection while the other received NACTRT. Over a mean follow-up period of 43 months, four patients developed recurrences. Two of them had local recurrence and only one had isolated local recurrence. ACM in resection margins of RC resection specimens does not seem to increase likelihood of local recurrence.

Mismatch-repair deficiency in solid tumors predicts their response to PD-1 blockade. Based on this principle, pembrolizumab is approved as standard of care for patients with unresectable or metastatic microsatellite instability-high (MSI-H) cancer. Despite this success, a large majority of metastatic colorectal cancer patients are not MSI-H and do not benefit from checkpoint blockade treatment. Predictive biomarkers to develop personalized medicines and guide clinical trials are needed for these patients. We, therefore, asked whether immunohistologic stratification of metastatic colorectal cancer based on primary tumor PD-L1 expression associated with the presence or absence of extracellular mucin defines a subset of metastatic colorectal cancer patients who exhibit a preexisting antitumor immune response and who could potentially benefit from the checkpoint blockade. To address this, we studied 26 advanced metastatic colorectal cancer patients treated with pembrolizumab (NCT01876511). To stratify patients, incorporation of histopathologic characteristics (percentage of extracellular mucin) and PD-L1 expression at the invasive front were used to generate a composite score, the CPM (composite PD-L1 and mucin) score, which discriminated patients who exhibited clinical benefit (complete, partial, or stable disease) from those patients with progressive disease. When validated in larger cohorts, the CPM score in combination with MSI testing may guide immunotherapy interventions for colorectal cancer patient treatment.

To evaluate the pattern of tumor relapse of pathological complete response (pCR) patients with locally advanced rectal cancer (LARC) following neoadjuvant chemoradiotherapy (nCRT) and total mesorectal excision (TME), and to identify predictive factors of distant metastasis in pCR patients after nCRT.

This was a retrospective analysis of 118 LARC patients who achieved a pCR following nCRT and TME from 2008 to 2015. Clinicopathological and therapeutic parameters were evaluated as possible predictors of distant metastasis-free survival (DMFS), and COX regression analysis was performed.

After a median follow-up of 57 months, the 5-year overall and disease-free survival rates were 94.7% and 88.1%, respectively. Overall, 6 patients (5.1%) died, no local recurrence occurred, 13 patients (11%) developed distant metastases, including lung (n = 5), liver (n = 2), bone (n = 3), lung and brain (n = 1), peritoneal (n = 1), and spleen (n = 1) metastasis. On univariate analysis, tumor distance from the anal verge (HR = 0.706, P = 0.039), acellular mucin pools (HR = 6.687, P = 0.002), and MUC1 expression (HR = 8.280, P < 0.001) were independently associated with DMFS. COX regression demonstrated that MUC1 expression (HR = 3.812, P = 0.041) remained to be an independent predictor of DMFS in pCR patients.

Distant metastasis still remained a major concern in pCR patients following nCRT and TME. Tumor distance from the anal verge, acellular mucin pools, and MUC1 expression were associated with distant metastasis in patients with pCR. MUC1 staining remained to be an independent risk factor for DMFS. Such information could facilitate treatment decision in these patients, such as adjuvant chemotherapy and follow-up.

Rectal cancer is prone to local recurrence and systemic metastasis. However, owing to improvements in TNM staging and treatment, including a more widespread use of rectal MRI and increased radiologist awareness of the key rectal cancer TNM staging features, the mortality rate of rectal cancer has been declining over the past few decades in adults over 50 years of age. Currently, rectal MRI plays a key role in the pre- and posttreatment evaluation of rectal cancer, assisting the multidisciplinary team in tailoring the most appropriate treatment option. The benefits achieved with rectal MRI are strictly dependent on obtaining good-quality images, which is important for the characterization of the main anatomic structures and their relationship with the tumor. In primary staging, rectal MRI helps the radiologist (a) describe the tumor location and morphology, (b) provide its T and N categories, (c) detect the presence of extramural vascular invasion, and (d) identify its relationship with surrounding structures, including the sphincter complex and involvement of the mesorectal fascia. These features help diagnose locally advanced rectal tumors (categories T3c-d, T4, N1, and N2), for which neoadjuvant chemoradiotherapy (CRT) is indicated. In restaging after neoadjuvant CRT, in addition to reassessing the features noted during primary staging, rectal MRI can help in the assessment of treatment response, especially with the emergence of nonsurgical approaches such as "watch and wait." ^©RSNA, 2019.

Neoadjuvant chemoradiation (NACR) is now standard of care in stage II and III rectal cancer. The advent of this modality of treatment has impacted on the way the pathological evaluation of resection specimens that have been subjected to preoperative chemoradiation is conducted. The gross description, sectioning and microscopic examination have had to be adapted to accommodate the changes induced by NACR. Attempts at introducing a uniform approach to the gross triaging and reporting of these specimens have been met with muted response. There still exists much variation in approach. The purpose of this overview is to highlight some of the newer developments and issues around NACR-treated rectal cancers from a pathological point of view. The NACR-treated resection specimens should be handled in a consistent manner, at least within individual institutions, if not universally. There should be generous sampling with multiple sections taken as tumour is often sequestered deep in the bowel wall. Microscopic examination should be extra vigilant as residual cancer can be present as single cells or small clusters, often deep in the muscularis propria or serosa. Acellular pools of mucin or non-viable tumour cells in mucin within the bowel wall or lymph nodes are not regarded as positive and do not upstage the tumour. The issue of grading of regression has been the subject of much debate, and several approaches have been published. It is recommended that a system that has clinical meaning and use to oncologists be used. Lymph node counts will be reduced after NACR, but reasonable attempts to accrue 12 nodes should be made.