Appendiceal goblet cell carcinoma: comparison of classification and staging systems with evaluation of the prognostic role of immunohistochemistry stains

Background: Goblet cell carcinoma (GCC) of the appendix is a unique lesion that exhibits features of both adenocarcinoma and neuroendocrine tumors. Due to the rarity of this cancer, multiple grading (e.g., Tang, Yozu, and Lee) and staging systems (e.g., tumor, lymph nodes, and metastasis [TNM]) have been developed for classification. This study aimed to compare commonly used classification systems and evaluate the prognostic effectiveness immunohistochemical staining may or may not have for appendiceal GCC. Methods: An electronic medical records review of patients who were diagnosed with GCC of the appendix in our hospital system from 2010 to 2020. The data were collected regarding the age at diagnosis, gender, initial diagnosis at presentation, operation(s) performed, final pathology results, current survival status, and year of recurrent disease or death year. Results: Ten patients were evaluated. Seventy percent of the patients were above the age of 50 years at diagnosis. Postdischarge survival ranged from 1 month to 109 months postdiagnosis. Two patients expired from GCC at 13- and 54-months following diagnosis. When comparing the classification systems, Lee categorized more patients as high risk than Tang and Yozu. Immunohistochemical staining was analyzed using four staining methods: Ki67, E-cadherin, Beta-catenin, and p53. Tumor, lymph nodes, and metastasis staging has supportive evidence for worsening prognosis and overall survival secondary to the depth of invasion of the tumor. Conclusion: Tumor, lymph nodes, and metastasis staging may be superior to the other classification systems in predicting overall mortality. Our study demonstrated that immunohistochemistry staining does not appear to have a significant impact in determining the prognosis for GCC of the appendix. (AU)

Comparison of model fit and discriminatory ability of M category as defined by the 7th and 8th editions of the tumor-node-metastasis classification of colorectal cancer and the 9th edition of the Japanese classification.

BACKGROUND: In transitioning from the 7th edition of the tumor-node-metastasis classification (TNM-7) to the 8th edition (TNM-8), colorectal cancer with peritoneal metastasis was newly categorized as M1c. In the 9th edition of the Japanese Classification of colorectal, appendiceal, and anal carcinoma (JPC-9), M1c is further subdivided into M1c1 (without other organ involvement) and M1c2 (with other organ involvement). This study aimed to compare the model fit and discriminatory ability of the M category of these three classification systems, as no study to date has made this comparison. METHODS: The study population consisted of stage IV colorectal cancer patients who were referred to the National Cancer Center Hospital from 2000 to 2017. The Akaike information criterion (AIC), Harrell's concordance index (C-index), and time-dependent receiver operating characteristic (ROC) curves were used to compare the three classification systems. Subgroup analyses, stratified by initial treatment year, were also performed. RESULTS: According to TNM-8, 670 (55%) patients had M1a, 273 (22%) had M1b, and 279 (23%) had M1c (87 M1c1 and 192 M1c2 using JPC-9) tumors. Among the three classification systems, JPC-9 had the lowest AIC value (JPC-9: 10546.3; TNM-7: 10555.9; TNM-8: 10585.5), highest C-index (JPC-9: 0.608; TNM-7: 0.598; TNM-8: 0.599), and superior time-dependent ROC curves throughout the observation period. Subgroup analyses were consistent with these results. CONCLUSIONS: While the revised M category definition did not improve model fit and discriminatory ability from TNM-7 to TNM-8, further subdivision of M1c in JPC-9 improved these parameters. These results support further revisions to M1 subcategories in future editions of the TNM classification system.

The 2019 World Health Organization Classification of appendiceal, colorectal and anal canal tumours: an update and critical assessment.

The recently published 5th edition 2019 World Health Organization (WHO) Classification of Tumours of the Digestive System brings significant changes from the 2010 4th edition. An emphasis on uniformity in nomenclature and grading for tumours across all organ systems is a particular feature of the 5th edition blue book series that is reflected in the gastrointestinal tract (GIT) classification. For example, simplified two tiered grading is reinforced for preinvasive lesions throughout the GIT, with dysplasia at all sites now being considered either low or high grade. Similarly, a uniform approach to classification and grading of GIT neuroendocrine neoplasms has been consolidated, with an emphasis on distinguishing grade 3 neuroendocrine tumours from neuroendocrine carcinomas. In this review, we discuss and critically assess the important and sometimes controversial changes made to the classification of tumours of the lower GIT, comprising the colorectum, vermiform appendix and anal canal. The particularly controversial decision to endorse the term 'sessile serrated lesion' for lesions previously termed 'sessile serrated polyp/adenoma' is explored. The morphological, molecular, and clinical insights behind the substitution of the term 'goblet cell adenocarcinoma' for 'goblet cell carcinoid' are assessed. The evolution of the classification of appendiceal mucinous neoplasms is considered. Inflammatory bowel disease related dysplasia and its evolving subtypes, with major implications for pathologists in routine practice, is explained.

Nomenclature of appendiceal mucinous lesions according to the 2019 WHO Classification of Tumors of the Digestive System.

BACKGROUND/AIMS: To analysis the appendiceal mucinous lesions according to the World Health Organization (WHO) 2019 classification of tumors of the digestive system (non-neuroendocrine tumors of the appendix vermiformis) MATERIALS AND METHODS: Clinical and histopathological data of 37 patients with histopathologically proven appendiceal mucinous lesion from January 2010 to May 2019 were evaluated retrospectively. Pathology slides were re-evaluated by two pathologists according to the WHO 2019 classification of tumors of the digestive system. RESULTS: Totally 37 patients (male:19 female: 18) aged 23 to 93 years were analyzed. Majority of the patients (75.7 %) had underwent appendectomy due to preliminary diagnosis of acute appendicitis (n=22) or periappendiceal tumoral lesions (n=9), the others (n=9) underwent incidental appendectomy. Whereas acute appendicitis was histopathologically diagnosed in 16 (43.2%) patients, perforation was diagnosed in 12 (32.4%) patients (perforation without appendicitis=3, perforation with appendicitis=6). According to the initial, pathology reports were prepared as follows: mucocele (n=10), mucinous cystadenoma (n=9), low-grade mucinous neoplasm (n=6), mucinous adenocarcinoma (n=5), mucosal hyperplasia (n=5), hyperplastic polyp (n=1), adenomatous polyp (n=1). On the basis of the WHO 2019 classification, pathology reports were prepared as follows: low-grade mucinous neoplasm (n=17), simple retention cysts (n=6), hyperplastic polyp (n=6), mucinous adenocarcinoma (n=5), ruptured appendiceal diverticula (n=2), sessile serrated lesion (n=1). CONCLUSION: The term of appendiceal mucinous lesion, which is recently introduced into medical literature is suitable to distinguish between lesions with and without malignancy potential. The WHO 2019 classification system has been an important step in simplifying the classification of non- neuroendocrine tumors of the appendix vermiformis.

Low-Grade Appendiceal Mucinous Neoplasms: A Single Institution Experience of 64 Cases With Clinical Follow-up and Correlation With the Current (Eighth Edition) AJCC Staging.

Background. In this single-institution study, we applied the current (eighth edition) American Joint Committee on Cancer pathologic staging criteria to 64 low-grade mucinous neoplasms of the appendix (LAMNs), examined their histopathologic features, and studied the patients' clinical outcomes. Design. Sixty-four LAMNs, with a median follow-up of 52 months, were reviewed. Results. The distribution of pathologic stages was pTis (n = 39), pT3 (n = 1), pT4a (n = 5), pT4aM1a (n = 8), and pT4aM1b (n = 11). Recurrence was observed in only 2 patients (both with pT4aM1b disease), one of whom died of disease. All remaining patients were disease-free after a median clinical follow-up of 60 months. Conclusions. Our study confirms that pTis LAMNs have an excellent prognosis and suggests that pT4a and pT4aM1a LAMNs may also have a low risk of developing progressive disease.

Introducing the eighth edition of the tumor-node-metastasis classification as relevant to colorectal cancer, anal cancer and appendiceal cancer: a comparison study with the seventh edition of the tumor-node-metastasis and the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma.

BACKGROUND: The eighth edition of the tumor-node-metastasis classification of malignant tumors updates cancer staging according to the evidence accumulated in the last 8 years since the release of the tumor-node-metastasis seventh edition. This review focuses on the new staging system. METHODS: The eight edition was compared with the seventh edition as well as the Japanese Classification of Colorcetal, Appendiceal, and Anal carcinoma ninth edition. RESULTS: Of colon and rectum, the tumor-node-metastasis eighth edition expands the M category. Specifically, colorectal cancer with peritoneal metastasis is newly categorized as M1c, distinguishing it from M1a (metastasis to one organ) and M1b (metastasis to more than one organ). In the ninth edition of Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma, M1c is further subdivided into M1c1 (metastasis to the peritoneum without other organ involvement) and M1c2 (metastasis to the peritoneum with other organ involvement). In the T category, the tumor-node-metastasis eighth edition excludes high-grade dysplasia (intraepithelial carcinoma) from Tis; this differs from both the tumor-node-metastasis seventh edition and the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma ninth edition. In the N category, the tumor-node-metastasis eighth edition does not add the number of tumor deposits to the number of positive regional lymph nodes, whereas this number is added in the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma ninth edition. The definition of anal cancer is also modified considerably in the tumor-node-metastasis eighth edition; specifically, tumors of perianal skin defined as within 5 cm of the anal margin are also classified as anal canal carcinoma, external iliac lymph nodes become regional lymph nodes, and both N2 and N3 are abolished in the N category. With regard to appendix, Tis (low-grade appendiceal mucinous neoplasma) and tumor deposit(s) are newly introduced. Finally, the tumor-node-metastasis eighth edition offers a new structure, labeled a 'prognostic factors grid', which consists of prognostic factors for survival in both colorectal and anal cancer. CONCLUSIONS: Staging classification is updated regularly, which clinicians should always catch up with.

Evaluation of appendiceal mucinous neoplasms with a new classification system and literature review.

Appendiceal mucinous neoplasms constitute a diagnostic spectrum ranging from adenoma to mucinous adenocarcinoma. To date, many classification systems have been proposed to reflect the histomorphological diversity of neoplasms in this range and their clinical correspondence, and also to form a common terminology between the pathologist and clinicians. The aim of this review is to provide an updated perspective on the pathological features of appendiceal mucinous neoplasms. Using the 2016 Modified Delphi Consensus Protocol (Delphi) and the Eighth Edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 19 cases presented from June 2011 to December 2016 were evaluated and diagnosed with appendiceal mucinous neoplasia. According to the Delphi, non-carcinoid epithelial tumours of the appendix were categorized in eight histomorphological architectural groups. These groups are adenoma, serrated polyp, low-grade appendiceal mucinous neoplasm, high-grade appendiceal mucinous neoplasm, mucinous adenocarcinoma, poorly-differentiated adenocarcinoma with signet-ring, signet-ring cell carcinoma and adenocarcinoma. The most common symptom was right lower quadrant pain. The median age of these cases was 60±15 years. There was a preponderance of females (F/M: 15/4). In our re-evaluation, six cases were diagnosed as serrated polyp. There were 11 cases in the LAMN group and two cases in the mucinous adenocarcinoma group. Using the Delphi and the AJCC manual, there were many changes in the classification, evaluation and treatment of appendiceal mucinous neoplasms. These classification systems have facilitated the compatibility and communication of clinicians and pathologists and have guided clinicians on treatment methods.

Histologic and Outcome Study Supports Reclassifying Appendiceal Goblet Cell Carcinoids as Goblet Cell Adenocarcinomas, and Grading and Staging Similarly to Colonic Adenocarcinomas.

Goblet cell carcinoid tumors are amphicrine tumors whose biological behavior ranges from indolent to highly aggressive, depending on tumor grade. Current grading systems for these tumors are based on identifying an adenocarcinoma arising in the setting of a goblet cell carcinoid tumor, which distinguishes this tumor from other gastrointestinal tract adenocarcinomas. Because goblet cell tumors are predominantly tumors of mucin secreting cells, we propose that they be classified as goblet cell adenocarcinomas, and graded using a methodology that has parallels in colorectal adenocarcinoma grading. We graded a large series of goblet cell adenocarcinomas by assessing the proportion of the tumor that demonstrates tubular or clustered growth. Histologic grade correlated with overall survival independent of stage, with median overall survival of 204, 86, and 29 months for low-grade, intermediate-grade, and high-grade goblet cell adenocarcinomas, respectively. Tumor stage also correlated with overall survival. We also graded the tumors according to previously proposed grading systems, and found that these systems are valid, in that they segregate patients according to prognosis.

Goblet cell carcinoid of the appendix - An interobserver variability study using two proposed classification systems.

Goblet cell carcinoid (GCC) is an uncommon tumor of the vermiform appendix. Due to a broad spectrum of morphological differentiation, subclassification and grading of GCCs remains an area of controversy. Two separate systems have proposed classifying GCC tumors into three (classical GCC; adenocarcinoma ex-GCC, signet ring cell type; adenocarcinoma ex-GCC, poorly differentiated carcinoma type) OR two subgroups (low and high grade GCC) based on morphological criteria. We independently compared the inter-observer variability associated with each classification system. Overall, both systems had moderate interobserver agreement, with the two-tiered system (κ=0.54) performing slightly better than the three-tiered system (κ=0.42). GI-specialist pathologists had substantial agreement for both two and three-tiered systems (κ=0.65 vs. 0.65). Non-GI trained pathologists had lower overall agreement than GI trained pathologists, but their agreement was better using the two-tiered system (κ=0.44) than the three-tiered system (κ=0.22). A sub-analysis of 6 cases with a high rate of discordant classification revealed several challenges that exist in applying current criteria, including differentiating "goblet" vs. "signet ring" cell morphology, applying a 1 mm2 criteria to multifocal non-contiguous glandular and single infiltrating cell architecture, differentiating fibro-inflammatory stroma from desmoplastic stroma, and solid architecture in cases with abundant extracellular mucin, and distinguishing "reactive" nuclear atypia from true "cytologic atypia". Despite these challenges, the study identified better agreement among GI pathologists than non-GI trained pathologists. While GI pathologist review may be helpful, further research on objective classification criteria remains an area of interest.

The histopathological classification, diagnosis and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinomas and pseudomyxoma peritonei.

The vermiform appendix is the primary site of several distinctive benign and malignant neoplasms. Some can produce the clinical syndrome of pseudomyxoma peritonei (PMP). A consensus on their terminology was reached by an international panel of pathologists and clinicians working under the auspices of the Peritoneal Surface Oncology Group International (PSOGI), and this review discusses the application of the PSOGI classification to routine reporting. We discuss diagnosis and differential diagnosis together with implications for patient management, covering low-grade appendiceal mucinous neoplasms, high-grade appendiceal mucinous neoplasms, serrated polyps, adenomas and adenocarcinomas. We do not cover goblet cell tumours or neuroendocrine neoplasms in this paper.

Appendiceal Mucinous Neoplasms: Diagnosis and Management.

OBJECTIVE: Appendiceal mucinous neoplasms (AMNs) are a rare and heterogeneous disease for which clinical management is challenging. We aim to review the literature regarding modalities of treatment to guide the management of AMNs. METHODS AND REVIEW CRITERIA: We conducted a PubMed search in February 2016 for English-language publications, using the terms "appendiceal," "appendix," "carcinoma," "cancer," "mucinous," "treatment," "genes," "target," "genomic," and terms listed in the articles' subheadings. Published reports and abstracts from the American Society of Clinical Oncology meetings were also searched. RESULTS: In this review, we summarize current data and controversies in AMN classification, clinical presentation, molecular alterations, treatment outcomes with regard to cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and the role of systemic chemotherapy. CONCLUSION: Appendiceal mucinous neoplasms are a heterogeneous group of tumors with a rising incidence. Treatment is based on stage and histology. Low-grade tumors are treated surgically with resection of the primary site in early stage disease, or peritoneal debulking and HIPEC in patients with advanced stage disease. Treatment of high-grade tumors requires further prospective trials, and options include debulking surgery and HIPEC with or without preoperative chemotherapy. Trials evaluating novel therapies based on the molecular profiling of AMN tumors are needed to evaluate therapeutic options in patients who are not surgical candidates. IMPLICATIONS FOR PRACTICE: This review provides a reference to guide gastroenterologists, pathologists, surgeons, and oncologists in the management of appendiceal mucinous neoplasms (AMNs), a rare and heterogeneous disease with no consensus on histologic classification or guidelines for treatment algorithms. This review summarizes all AMN classifications and proposes a treatment algorithm based on stage and histology of disease.

Overinterpretation is common in pathological diagnosis of appendix cancer during patient referral for oncologic care.

CONTEXT: Low-grade appendiceal mucinous neoplasm (LAMN) and appendiceal adenocarcinoma are known to cause the majority of pseudomyxoma peritonei (PMP, i.e. mucinous ascites); however, recognition and proper classification of these neoplasms can be difficult despite established diagnostic criteria. OBJECTIVE: To determine the pathological diagnostic concordance for appendix neoplasia and related lesions during patient referral to an academic medical center specialized in treating patients with PMP. DESIGN: The anatomic pathology laboratory information system was searched to identify cases over a two-year period containing appendix specimens with mucinous neoplasia evaluated by an outside pathology group and by in-house slide review at a single large academic medical center during patient referral. RESULTS: 161 cases containing appendix specimens were identified over this period. Forty-six of 161 cases (28.6%) contained appendiceal primary neoplasia or lesions. Of these, the originating pathologist diagnosed 23 cases (50%) as adenocarcinoma and 23 cases (50%) as LAMN; however, the reference pathologist diagnosed 29 cases (63.0%) as LAMN, 13 cases (28.3%) as adenocarcinoma, and 4 cases (8.7%) as ruptured simple mucocele. Importantly, for cases in which the originating pathologist rendered a diagnosis of adenocarcinoma, the reference pathologist rendered a diagnosis of adenocarcinoma (56.5%, 13 of 23), LAMN (39.1%, 9 of 23), or simple mucocele (4.3%, 1 of 23). The overall diagnostic concordance rate for these major classifications was 71.7% (33 of 46) with an unweighted observed kappa value of 0.48 (95% CI, 0.27-0.69), consistent with moderate interobserver agreement. All of the observed discordance (28.3%) for major classifications could be attributed to over-interpretation. In addition, the majority of LAMN cases (65.5%) had potential diagnostic deficiencies including over-interpretation as adenocarcinoma and lacking or discordant risk stratification (i.e. documentation of extra-appendiceal neoplastic epithelium). CONCLUSIONS: Appendiceal mucinous lesions remain a difficult area for appropriate pathological classification with substantial discordance due to over-interpretation in this study. The findings highlight the critical need for recognition and application of diagnostic criteria regarding these tumors. Recently published consensus guidelines and a checklist provided herein may help facilitate improvement of diagnostic concordance and thereby reduce over-interpretation and potential overtreatment. Further studies are needed to determine the extent of this phenomenon and its potential clinical impact.

Are goblet cell carcinoids a group of heterogeneous tumors?

BACKGROUND: Goblet cell carcinoids belong to neuroendocrine tumors, according to the WHO classification. The tumors are diagnosed based on a typical histological pattern and using neuroendocrine markers. However, some tumors do not react with these markers and yet expression of proliferative markers is high. Do these tumors belong to G1 and G2 neuroendocrine tumors? METHODS: The sample comprised nine cases of tumors of the appendix identified by immunohistological methods as goblet cell carcinoids or adenocarcinoma ex goblet cell carcinoid. RESULTS: In six cases, hematoxylin and eosin staining revealed tumors completely or 90% made of characteristic large tumor cells observed in typical goblet cell carcinoids. The remaining three cases were identified as adenocarcinomas arising ex goblet cell carcinoids. Immunohistological examination revealed that in four cases of typical goblet cell carcinoids, expression of neuroendocrine markers was low or completely negative. Yet in two cases, the Ki-67 proliferative index exceeded the 20% cut-off for inclusion in the G1 and G2 category. CONCLUSIONS: Goblet cell carcinoids are a heterogeneous group of tumors that may express neuroendocrine markers in a small number of tumor cells or are negative to these markers. However, high expression of the proliferative marker Ki-67 exceeds the criteria for G1 and G2 neuroendocrine tumors. It is our opinion that these tumors may be classified as a specific type of carcinoma.

Appendiceal goblet cell carcinoid: common errors in staging and clinical interpretation with a proposal for an improved terminology.

Goblet cell carcinoid (GCC) is staged and treated as adenocarcinoma (AC) and not as neuroendocrine tumor (NET) or neuroendocrine carcinoma. The term carcinoid may lead to incorrect interpretation as NET. The aim of the study was to explore pitfalls in staging and clinical interpretation of GCC and mixed GCC-AC, and propose strategies to avoid common errors. Diagnostic terminology, staging, and clinical interpretation were evaluated in 58 cases (27 GCCs, 31 mixed GCC-ACs). Opinions were collected from 23 pathologists using a survey. Clinical notes were reviewed to assess the interpretation of pathology diagnoses by oncologists. NET staging was incorrectly used for 25% of GCCs and 5% of mixed GCC-ACs. In the survey, 43% of pathologists incorrectly indicated that NET staging is applicable to GCCs, and 43% incorrectly responded that Ki-67 proliferation index is necessary for GCC grading. Two cases each of GCC and mixed GCC-AC were incorrectly interpreted as neuroendocrine neoplasms by oncologists, and platinum-based therapy was considered for 2 GCC-AC cases because of the mistaken impression of neuroendocrine carcinoma created by use of the World Health Organization 2010 term mixed adenoneuroendocrine carcinoma. The term carcinoid in GCC and use of mixed adenoneuroendocrine carcinoma for mixed GCC-AC lead to errors in staging and treatment. We propose that goblet cell carcinoid should be changed to goblet cell carcinoma, whereas GCC with AC should be referred to as mixed GCC-AC with a comment about the proportion of each component and the histologic subtype of AC. This terminology will facilitate appropriate staging and clinical management, and avoid errors in interpretation.

Neuroendocrine, goblet cell and mixed adeno-neuroendocrine tumours of the appendix: updates, clinical applications and the future.

INTRODUCTION: Appendiceal neuroendocrine neoplasms are rare, clinically challenging tumours that are typically incidentally diagnosed, have a poorly understood biology and have controversy surrounding their management. Most are adequately treated with appendectomy, and although distant metastases are rare, the threat of disease dissemination remains and current guidelines possess poor accuracy in terms of selecting patients requiring more extensive surgery, i.e. oncological right-hemicolectomy. Areas covered: In this article, we discuss the presentation and diagnostic work-up of patients with appendiceal neuroendocrine neoplasms, and also examine the evidence base for existing management strategies. We highlight controversies within the management of these tumours, and anticipate avenues for further progress. Although no longer classified as neuroendocrine neoplasms, we also discuss two related forms of tumours with neuroendocrine features - goblet cell cancers and mixed adeno-neuroendocrine carcinomas. Expert commentary: Existing guidelines for the treatment of appendiceal neuroendocrine neoplasms are derived from a limited evidence base and are unable to accurately predict which patients require extensive attempts at surgical disease control. Future advances in the field of improved patient selection for more extensive surgery may be possible with multi-factorial tumour assessment integrating morphological and molecular analyses.

Curative Surgical Resection as a Component of Multimodality Therapy for Peritoneal Metastases from Goblet Cell Carcinoids.

BACKGROUND: The impact of histopathologic features on oncologic outcomes for patients with peritoneal metastases from goblet cell carcinoid (GCC) undergoing multimodality therapy, including cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC), is unknown. METHODS: This study prospectively analyzed 43 patients with GCC undergoing CRS-HIPEC between 2005 and 2013. Pathology slides were re-reviewed to classify GCC into histologic subtypes according to the Tang classification. Kaplan-Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes. RESULTS: The 43 patients in this study underwent 50 CRS-HIPEC procedures for peritoneal metastases from GCC, and the majority received neoadjuvant and/or adjuvant systemic chemotherapy. The GCC demonstrated an aggressive phenotype with frequent lymph node and peritoneal metastases without systemic dissemination. The majority of the patients had Tang B GCC. The estimated median overall survival times after surgery for the patients with Tang A, B, and C GCC were respectively 59, 22, and 13 months. In a multivariate Cox-regression analysis, poor survival was associated with patients who had Tang B or C GCC, those undergoing incomplete macroscopic resection, and those with symptoms at the time of CRS-HIPEC. The patients with Tang A GCC demonstrated oncologic outcomes similar to those with intermediate-grade (American Joint Committee on Cancer [AJCC] grade 2) disseminated mucinous appendiceal neoplasms, whereas the patients with Tang B and C GCC demonstrated survival rates similar to or worse than those with high-grade (AJCC grade 3) disseminated mucinous appendiceal neoplasms. CONCLUSIONS: Tang classification is an independent prognostic factor for poor survival after multimodality therapy for GCC. Patients with Tang C GCC demonstrate limited survival and are not ideal candidates for a surgical approach.

Linfoma del apéndice cecal con presentación clínica de apendicitis aguda: a propósito de un caso / Lymphoma of the appendix with clinical presentation of acute appendicitis. A case report

Antecedentes: Las neoplasias apendiculares estan presentes en menos del 1% de las apendicectomías. Los linfomas primarios del apéndice son raros ocurriendo en 0.015% de todos los linfomas gastrointestinales. La edad promedio para diagnóstico de los linfomas gastrointestinales es 55 años. En el apéndice cecal se encuentran en la segunda y tercera década de la vida. Es más común en hombres. La manifestación más común es la apendicitis aguda secundaria a obstrucción luminal. Caso clínico: Este es el primer caso reportado en la literatura hondureña. Se trata de una paciente de 67 años que ingresa al Hospital Escuela Universitario de Tegucigalpa, Honduras, con cuadro de dolor abdominal de dos semanas de evolución y sepsis por peritonitis generalizada secundaria a apendicitis aguda complicada. En el transoperatorio se identifican hallazgos compatibles con mucocele pero en la biopsia se diagnostica linfoma difuso de células grandes. El estudio inmunohistoquímico revela positividad para CD20. La evolución postoperatoria de la paciente fue tórpida hacia falla multiorgánica y los familiares decidieron exigir el alta para retornar a su lugar de origen. Conclusión: Aunque las neoplasias apendiculares son infrecuentes, siempre es necesario tener presente el diagnóstico al momento de realizar una apendicectomía, puesto que esto cambia el pronóstico y tratamiento...(AU)

A Consensus for Classification and Pathologic Reporting of Pseudomyxoma Peritonei and Associated Appendiceal Neoplasia: The Results of the Peritoneal Surface Oncology Group International (PSOGI) Modified Delphi Process.

Pseudomyxoma peritonei (PMP) is a complex disease with unique biological behavior that usually arises from appendiceal mucinous neoplasia. The classification of PMP and its primary appendiceal neoplasia is contentious, and an international modified Delphi consensus process was instigated to address terminology and definitions. A classification of mucinous appendiceal neoplasia was developed, and it was agreed that "mucinous adenocarcinoma" should be reserved for lesions with infiltrative invasion. The term "low-grade appendiceal mucinous neoplasm" was supported and it was agreed that "cystadenoma" should no longer be recommended. A new term of "high-grade appendiceal mucinous neoplasm" was proposed for lesions without infiltrative invasion but with high-grade cytologic atypia. Serrated polyp with or without dysplasia was preferred for tumors with serrated features confined to the mucosa with an intact muscularis mucosae. Consensus was achieved on the pathologic classification of PMP, defined as the intraperitoneal accumulation of mucus due to mucinous neoplasia characterized by the redistribution phenomenon. Three categories of PMP were agreed-low grade, high grade, and high grade with signet ring cells. Acellular mucin should be classified separately. It was agreed that low-grade and high-grade mucinous carcinoma peritonei should be considered synonymous with disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis, respectively. A checklist for the pathologic reporting of PMP and appendiceal mucinous neoplasms was also developed. By adopting the classifications and definitions that were agreed, different centers will be able to use uniform terminology that will allow meaningful comparison of their results.

The 7th Edition of the AJCC Staging Classification Correlates with Biologic Behavior of Mucinous Appendiceal Tumor with Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC).

PURPOSE: We evaluated the 7th edition of the American Joint Committee on Cancer (AJCC) staging classification in terms of overall survival (OS) in patients with PMP treated with cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A total of 208 PMP patients treated with CRS/HIPEC were identified from a prospective database. Patients with peritoneal mucinous carcinomatosis (PMCA) were retrospectively staged at time of diagnosis according to AJCC staging classification. Patients with disseminated peritoneal adenomucinosis (DPAM) were evaluated in a separate group. RESULTS: Median follow-up was 5.2 years. Of 208 patients, 124 had PMCA and 84 patients had DPAM. According to the AJCC staging classification 47 lymph node (LN) negative patients with well-differentiated PMCA, were classified as a stage IVA. 77 patients with either moderately or poorly differentiated PMCA irrespective of LN status, or well-differentiated PMCA with positive LN were classified as stage IVB. 84 patients with DPAM, constituted a separate group. OS of stage IVA and IVB patients was 100, 90, 67, and 91, 50, and 27 for 1, 3, and 5 years, respectively (p < 0.001). OS of DPAM patients was 96, 90, and 88 % for 1, 3, and 5 years, respectively (p = 0.025 comparing to IVA). PFS was estimated for IVA and IVB PMCA patients who were considered disease free after CRS/HIPEC and was 78, 52, and 43 % in the IVA patients and 65 %, 15 %, and 0 in the IVB group at 1, 3, and 5 years, respectively (p = 0.004). The adjusted HR for AJCC stages (IVA/IVB) was 3.7 (95 % confidence interval 2.0-6.7) (p < 0.001). CONCLUSIONS: The 7th edition of the AJCC staging classification is a simple, reproducible, and valid classification for staging patients with PMCA undergoing CRS/HIPEC.