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Mucinous Appendiceal Neoplasms: Classification, Imaging, and HIPEC

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Mucinous Appendiceal Neoplasms: Classification, Imaging, and HIPEC Abdominal Radiology (2019) 44:1686–1702 https://doi.org/10.1007/s00261-018-01888-y REVIEW PAPER Mucinous appendiceal neoplasms: classifcation, imaging, and HIPEC David J. Bartlett1 · Paul G. Thacker Jr.1 · Travis E. Grotz2 · Rondell P. Graham3 · Joel G. Fletcher1 · Wendaline M. VanBuren1 · Veena R. Iyer1 · Jef L. Fidler1 · Christine O. Menias4 · Nabil Wasif5 · Shannon P. Sheedy1 Published online: 4 January 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Recent advances, specifcally cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), ofer advantages compared to the traditional therapeutic approach of systemic chemotherapy in the treatment of peritoneal carci- nomatosis from mucinous appendiceal neoplasms (MAN). This review provides an up-to-date, comprehensive summary of the histologic classifcation of MAN, reviews common imaging fndings of mucoceles and pseudomyxoma peritonei, and describes the radiologist’s role in the multidisciplinary care team in quantifying disease and in helping select patients for defnitive surgery. Keywords Mucinous appendiceal neoplasm, MAN · Hyperthermic intraperitoneal chemotherapy, HIPEC · Cytoreductive surgery · Pseudomyxoma peritonei, PMP Introduction “peritoneal surface malignancies” (PSM) as they share a common clinical evolution and treatment. On the basis of Peritoneal carcinomatosis (PC) results from direct spread the epidemiological data, PSM have a high annual incidence, or metastasis to the visceral and parietal peritoneum by a including nearly 30% of gastric cancers, 13% of colorec- variety of tumors originating from the abdominal organs, tal cancers, 60% of ovarian cancers, nearly all appendiceal or less commonly from the peritoneal lining itself. This adenocarcinomas, and peritoneal mesothelioma [1–3]. heterogeneous group of tumors is encompassed in the term In the past, systemic chemotherapy alone was employed for palliative intent of PSM. However, in the mid-1990s, thanks to the peritoneal malignancy surgical expert Paul Meeting presentation: This topic was presented as an educational Sugarbaker’s pioneering eforts, research began into devel- exhibit (# 95) at the 2018 Society of Abdominal Radiology Annual oping an integrated therapy for PSM. This integrated thera- Meeting. Cum Laude award. peutic scheme, termed cytoreductive surgery/hyperthermic Electronic supplementary material The online version of this intraperitoneal chemotherapy (CRS/HIPEC), includes a article (https​://doi.org/10.1007/s0026​1-018-01888​-y) contains systematic intraoperative evaluation of the abdomen with supplementary material, which is available to authorized users. aggressive resection of all visible tumor while preserving organs whenever possible, i.e., CRS, and high-dose intra- * Shannon P. Sheedy [email protected] peritoneal chemotherapy with intraperitoneal hyperthermia (HIPEC) [4–10]. Although CRS/HIPEC is the only efective 1 Department of Radiology, Mayo Clinic, 200 First Street SW, treatment for patients with peritoneal carcinomatosis from Rochester, MN 55905, USA appendiceal neoplasms, it carries high risk of morbidity. 2 Department of Hepatobiliary and Pancreatic Surgery, Mayo Thus, correct patient selection for the procedure is critical Clinic, Rochester, MN, USA and requires multidisciplinary collaboration. In this review, 3 Department of Laboratory Medicine and Pathology, Mayo we will discuss the pathologic classifcation and radiologic Clinic, Rochester, MN, USA appearance of epithelial appendiceal neoplasms, describe 4 Department of Radiology, Mayo Clinic, Scottsdale, AZ, USA the CRS/HIPEC procedure, and help defne the role of the 5 Department of General Surgery, Mayo Clinic, Scottsdale, radiologist in the multidisciplinary team. AZ, USA Vol:.(1234567890)1 3 Abdominal Radiology (2019) 44:1686–1702 1687 Mucinous appendiceal neoplasm with minimal atypia and may be more likely to develop PMP than the poorly diferentiated adenocarcinoma that Appendiceal neoplasms are relatively rare, reported in less shows little or no gland formation [15, 16]. Because of than 1% of appendectomy specimens [11, 12]. Epithelial their worse prognosis, poorly differentiated mucinous appendiceal neoplasms, about 70% of which are mucinous neoplasms with signet ring cells are classifed separately histologic type, and neuroendocrine neoplasms account [20–22]. The non-mucinous appendiceal adenocarcinoma for the majority of primary appendiceal tumors [11, 13, is more similar histologically and radiologically to colo- 14]. The majority of mucinous appendiceal neoplasms rectal adenocarcinomas, often presenting with a focal (MANs) develop in middle-aged and elderly patients and soft tissue mass and with greater propensity to develop are discovered incidentally, but some patients present with regional lymph node metastases and metastases to liver, non-specifc signs or symptoms such as abdominal pain lung, and peritoneum [13]. or distension. MANs are the most common cause of pseu- Although PMP does not generally metastasize to lymph domyxoma peritonei (PMP), a clinical syndrome charac- nodes or beyond the peritoneal cavity, especially in its low- terized by progressive accumulation of mucinous tumor grade form, it should be considered malignant as it is char- throughout the peritoneal cavity [15]. acterized by relentless progression and will become fatal if In 2016, in an attempt to achieve consistency and to ena- not treated. The PSOGI expert panel recommends that PMP ble more meaningful data sharing across institutions, the classifcation be based on the histology of the peritoneal Peritoneal Surface Oncology Group International (PSOGI) disease, rather than based on the primary neoplasm [16]. issued a consensus statement regarding the nomenclature The panel proposed the following categories and associated and classifcation of epithelial appendiceal neoplasms and grading scheme (G1–G3) [16]: PMP. According to the new consensus statement, mucinous neoplasms (excluding the goblet cell tumor, a subtype of • Acellular mucin—characterized by the absence of neuroendocrine tumor which also has features of mucinous neoplastic epithelial cells within the peritoneal mucin neoplasm) are classifed as follows [16]: (Fig. 1a) • Low-grade mucinous carcinoma peritonei—G1 (previ- • LAMN (low-grade appendiceal mucinous neoplasm)— ously referred to as disseminated peritoneal adenomuci- extends beyond the mucosa into the appendiceal wall nosis [DPAM]) but without infltrative invasion and with low-grade • High-grade mucinous carcinoma peritonei—G2 (previ- cytologic atypia ously referred to as peritoneal mucinous carcinomatosis • HAMN (high-grade appendiceal mucinous neo- [PMCA]) plasm)—extends beyond the mucosa into the appen- • High-grade mucinous carcinoma peritonei with signet diceal wall but without infltrative invasion and with ring cells—G3 (previously referred to as peritoneal muci- high-grade cytologic atypia nous carcinomatosis with signet ring cells [PMCA-S]) • Mucinous adenocarcinoma—shows infltrative invasion (Fig. 1b) and may be well, moderately, or poorly diferentiated • Poorly diferentiated mucinous adenocarcinoma with Because of the distinct natural history and prognosis of signet ring features MAN, the TNM classifcation system is similar to, but inde- pendent of, the colorectal staging system (Online Appendix The specifc histology of the appendiceal neoplasms A) [23, 24]. predicts the biologic behavior and the penchant for specifc patterns of disease spread [11]. Regardless of the degree of cellular atypia, both LAMN and HAMN can develop Imaging of mucinous appendiceal neoplasm transmural extension or can rupture, and when this occurs, and pseudomyxoma peritonei the patient is at risk for developing PMP. The presence of epithelial cells within the extra-appendiceal mucin The general descriptor “appendiceal mucocele” refers to portends a worse prognosis; thus, any extra-appendiceal the presence of a mucin flled, dilated appendix (Fig. 2). mucin must be carefully inspected in appendectomy speci- The mucocele etiology may be neoplastic, most commonly mens. Limited data suggests that HAMN is more likely to related to MAN, or non-neoplastic. Non-neoplastic etiolo- be associated with extra-appendiceal epithelial cells than gies such as mucosal hyperplasia or a simple retention cyst is LAMN [17–19]. as a result of luminal obstruction, e.g., from an appendi- A well-diferentiated mucinous adenocarcinoma con- colith, only account for about 20% of mucoceles [25]. The sists of mostly mucin pools lined by neoplastic epithelium imaging diagnosis of a MAN rests on the identifcation of the mucocele, and the presence of a mucocele should impel 1 3 1688 Abdominal Radiology (2019) 44:1686–1702 Fig. 1 a This photomicrograph illustrates acellular mucin. b In con- trast, this photomicrograph shows signet ring cells (arrows) with their characteristic cytomorphology dispersed in mucin. When this is identifed in the peritoneum, this confrms the diagnosis of peritoneal mucinous carcinomatosis with signet ring cells an investigation for extra-appendiceal mucin. Only when the mucin is distributed in the peritoneal cavity beyond the right lower quadrant periappendiceal region, the patient is consid- ered to have PMP. The prospective suggestion of MAN or PMP on imaging may help the patient receive appropriate initial care and prevent the potential need for a second, more extensive surgery, which may be required when neoplasm is Fig. 2 A 55-year-old female found to have a mucocele on CT
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