Article ID: 24-00051
We report two cases of low-grade appendiceal mucinous neoplasm (LAMN) mimicking ovarian tumors that were treated with laparoscopic surgery.
Case 1: A 57-year-old woman was referred to our hospital because of a pelvic mass noted during physical examination. Imaging revealed an oval, cystic, 81×39-mm mass diagnosed as a right ovarian tumor, and surgery was performed. Intraoperative findings revealed an appendiceal tumor, and laparoscopic appendectomy was conducted. The pathological diagnosis was LAMN.
Case 2: A 76-year-old woman was referred to our hospital because of a pelvic mass noted during physical examination. Imaging revealed an oval, cystic, 36×23-mm mass in the pelvic cavity, which was suspected to be a right ovarian tumor. Since it was slightly displaced to the cephalic side, surgery was performed with the possibility of a gastrointestinal tumor in mind. Intraoperative findings revealed an appendiceal tumor, and a laparoscopic appendectomy was conducted. The pathological diagnosis was LAMN.
LAMN is a rare lesion with a risk of serious complications if the appendiceal wall ruptures and the tumor extends beyond the appendix. Although its preoperative diagnosis is challenging, it is important that gynecologists differentiate it from adnexal tumors.
LAMN is a rare disease that consists of a single layer of columnar epithelial cells with low-grade atypia, and presents as a cystic dilation of the appendiceal lumen with mucus retention1). Histologically, it is an adenoma-like tumor, but it can rupture and seed neoplastic epithelium into the peritoneum, leading to pseudomyxoma peritonei (PMP), a serious complication with high morbidity and mortality rates2). In this study, we report two cases of appendiceal tumors that were diagnosed during surgery performed for masses preoperatively assumed to be ovarian tumors, with successful treatment by laparoscopic appendectomy. We also discuss the differential diagnosis of these tumors.
A 57-year-old woman visited a urology clinic because of a positive urine protein test identified during a medical checkup. She was referred to our department after ultrasonography revealed a cystic mass in her pelvis. She had no abdominal pain. Transvaginal ultrasonography revealed an oval, cystic, 81×39-mm tumor on the right side of the pelvic cavity (Figure 1A). On magnetic resonance imaging (MRI), the tumor showed high signal intensity on T2-weighted imaging (WI), low signal intensity on T1WI, and no fat suppression. A normal right ovary was identified adjacent to the tumor (Figure 1B-F). The tumor marker CEA was elevated at 14.2 ng/ml. Other tumor markers were within normal limits (CA125:17.5 U/ml, CA199: 32.7 U/ml). Laparoscopic surgery was performed with a preoperative diagnosis of an adnexal tumor (a serous or mucinous ovarian or paraovarian cyst was suspected). The surgical findings showed that the bilateral ovaries were normal in size and the mass was an appendiceal tumor, and a laparoscopic appendectomy was carried out by a surgeon (Figure 2). The intraoperative cytological examination of the ascites fluid was negative. The postoperative pathological diagnosis was LAMN, with no perforations and with negative margins (Figure 3a).
Preoperative imaging findings from Case 1.
Transvaginal ultrasonography revealed an oval, cystic, 81×39-mm tumor on the right side of the pelvic cavity (A). On magnetic resonance imaging (MRI), the tumor appeared to have high signal intensity on T2 weighted imaging (WI), low signal intensity on T1WI, and no fat suppression. A right normal ovary was also identified adjacent to the tumor (E, F, yellow arrow).
Laparoscopic findings from Case 1.
Laparoscopic findings showed that the bilateral ovaries were normal in size (A) and the mass was an appendiceal tumor (B, C, D). Laparoscopic appendectomy was performed (E, F).
Histopathological findings from Cases 1 and 2.
In both Case 1 and 2, the appendix was oval and swollen with a lumen filled with yellowish mucus, and the wall was thinning or fibrosclerotic (A, B, E, F). In both Case 1 and 2, the mucosa showed proliferation of tumor cells composed of mucus-producing columnar epithelium that developed in a flat or micropapillary fashion with poor atypia, with a histological diagnosis of low-grade appendiceal mucinous neoplasm (LAMN) (C, G). In Case 1, although a portion of the wall was indurated due to mucus retention and the tumor cells were absent, the growth of LAMN persisted in the muscularis propria (MP), and on the basis of its depth it was diagnosed as pT2 (MP) (D). In Case 2, although tumor cells were absent in part of the wall and granulation tissue had formed, with wall destruction and thinning, a minimal amount of MP was preserved, and LAMN was diagnosed as pT2 (MP) (H).
HE stain: Hematoxylin-Eosin stain. EM stain: Elastica-Masson stain.
A 76-year-old woman was referred to our department after abdominal ultrasonography during a medical checkup revealed an abdominal tumor. She had no abdominal pain. Transvaginal ultrasonography revealed an oval, cystic, 36×23-mm tumor on the right side of the pelvic cavity with no ascites (Figure 4A). Contrast-enhanced MRI showed high signal intensity on T2WI, low signal intensity on T1WI, no fat suppression, and no contrast effect (Figure 4b-e). Contrast-enhanced CT showed calcification in part of the tumor wall (Figure 4f). Tumor markers were all within normal limits (CEA:3.4 ng/ml, CA125:10.3 U/ml, CA199:8.5 U/ml). A right ovarian tumor (serous or mucinous cystadenoma) was suspected;however, since the tumor was slightly displaced to the cephalic side, the patient was referred to a gastroenterologist, who performed a colonoscopy. This revealed no abnormal findings, and there was no diagnosis of a gastrointestinal tumor. Laparoscopic surgery was performed with a preoperative diagnosis of an adnexal tumor. Surgical findings showed that the bilateral ovaries were normal in size, and the mass was an appendiceal tumor. Laparoscopic appendectomy was conducted by a surgeon (Figure 5). The intraoperative cytological examination of the ascites fluid was negative. The postoperative pathological diagnosis was LAMN, with no perforations and with negative margins (Figure 3b).
Both patients have been followed up by surgeons and have shown no signs of recurrence to date.
Preoperative imaging findings from Case 2.
Transvaginal ultrasonography revealed an oval, cystic, 36×23-mm tumor on the right side of the pelvic cavity (A). Contrast-enhanced magnetic resonance imaging (MRI) showed that the tumor (yellow arrow) had high signal intensity on T2 weighted imaging (WI) (B, C), low signal intensity on T1WI (D), and no fat suppression (E). Contrast-enhanced computed tomography (CT) showed an oval tumor (F, G, H) with calcification in part of the tumor wall (F, white arrow).
Laparoscopic findings from Case 2.
Laparoscopic findings showed that the bilateral ovaries were normal in size (A, B) and the mass was an appendiceal tumor (C, D). Laparoscopic appendectomy was performed (E, F).
Appendiceal tumors are rare lesions that account for fewer than 1% of all gastrointestinal neoplasms3,4), and are often found incidentally in tissue removed for the diagnosis of appendicitis, reportedly in approximately 1% of resected specimens4-7). A cohort study conducted in Japan reported that of 760 appendiceal tumors, 515 (67.8%) were mucinous carcinomas and 245 (32.2%) were non-mucinous carcinomas, and of the former, 267 (35.1%) were LAMN8).
Histologically, LAMN is an adenoma-like tumor with low-grade atypia;however, if it extends beyond the appendix, it can develop into PMP, which has extremely high morbidity and mortality rates. LAMN is categorized as a carcinoma by the World Health Organization (WHO) classification because of its malignant biological behavior1,2,9). In the WHO classification, the term “mucinous cystadenoma” was deleted in 2016, and this entity was instead classified into LAMN and high-grade appendiceal mucinous neoplasm (HAMN) with high-grade cytological atypia9,10). To achieve consistency with the WHO classification, the same terminology has been adopted and it is described as a subtype of adenocarcinoma in the Japanese Classification of Colorectal, Appendiceal, and Anal Carcinoma11).
The clinical symptoms of unruptured LAMN are nonspecific, and the condition is often asymptomatic and is discovered incidentally during follow-up or close examination of other diseases10). There are several reports of cases that were preoperatively misidentified as adnexal tumors and diagnosed during gynecologic surgery, as in our cases6,10). It is well known that LAMN can rupture and seed mucin and neoplastic epithelium into the peritoneum, leading to PMP, a serious complication characterized by intraperitoneal accumulation of mucinous tumors and ascites. Although PMP is a very rare disease with an incidence of 1 in 1 million, it has a poor prognosis and its cure requires highly invasive, multidisciplinary treatment. Therefore, timely identification and treatment of LAMN are crucial for reducing PMP risk and improving prognosis2,3,12).
Most cases of PMP originate from LAMN, and those of ovarian origin are rather rare. Of PMP cases experienced at our department, three of four were derived from LAMN, and the other originated from the ovary (no tumor was found in the removed appendix)12). Interestingly, women with PMP often exhibit marked ovarian enlargement due to metastatic mucinous tumors, even those of appendiceal origin, and the ruptured appendix is rather small, making preoperative and intraoperative diagnosis difficult. In such cases, surgery is often performed due to rupture of a mucinous ovarian tumor, and postoperative immunostaining can then identify the origin of PMP12).
Although it remains quite difficult to diagnose LAMN preoperatively, it is important to differentiate it from adnexal tumors in cases of right-sided pelvic masses. Yu et al. stated that CT imaging is useful in the diagnosis of LAMN, and that findings that may indicate LAMN include a well-defined oval mass with a slightly higher density than a serous tumor, an irregularly thickened cyst wall with contrast-enhancement and calcification of the curved wall13). LAMN should also be kept in mind in elderly women with any of these findings and non-specific symptoms resembling appendicitis13).
The characteristic findings of LAMN on ultrasonography, such as a cystic mass with concentric echogenic layers within the tumor (“onion skin sign”), the confirmation of normal ovaries, and the separate movement of the tumor and ovaries upon compression with the ultrasound probe (“split sign”), have also been reported as findings that suggest a non-ovarian tumor and should raise suspicion for LAMN2,10).
The principal treatment for LAMN is early surgical excision before the cyst wall ruptures2). Although there are no clear criteria regarding resection technique or extent, the Clinical Practice Guidelines of the American Society of Colon and Rectal Surgeons state that an appendectomy is generally acceptable for managing LAMN that is shown to be confined to the appendix on pathological examination (negative surgical margins and no serosal invasion)2,14). Wang et al. developed an algorithm for the treatment of LAMN and reported that the combination of appendectomy plus PMP surveillance via postoperative CT was sufficient if the appendectomy margins involved mucin or neoplastic epithelium, or if there was ruptured LAMN without peritoneal dissemination and the mucus accumulation was confined to the right lower abdominal quadrant2,15). Once LAMN progresses to PMP, the patient requires aggressive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy2,12,16). Laparoscopic surgery for LAMN confined to the appendix has also been reported to have similar results to open surgery in terms of long-term prognosis17). Minimally invasive surgery may be preferable for the patient when possible, as in our two cases.
In Case 1 in the present study, although MRI showed a normal ovary adjacent to an oval tumor, surgery was performed without considering the possibility of a non-adnexal tumor (suspected paraovarian cyst or cystic fallopian tube tumor). In Case 2, the possibility of a gastrointestinal tumor was suspected on the basis of our experience with Case 1;however, no appendiceal tumor was identified, and laparoscopic surgery was performed with a preoperative diagnosis of an ovarian tumor. In addition, Case 2 was characterized by several findings suspicious of LAMN when viewed retrospectively (an oval tumor with wall calcification, location, etc.). Since this was a small, simple cystic tumor without symptoms, the patient was considered for observation first. However, surgery was performed because the patient wished to have surgery, after fully explaining the risks and benefits of surgery and follow-up observation, and as a result, progression to PMP was prevented. Both cases are thought to be highly instructive for gynecologists.
We present two cases which serve as a reminder of the difficulty of preoperative diagnosis of LAMN. LAMN is a rare disease that often has nonspecific clinical manifestations and can sometimes be asymptomatic. There have been scattered case reports of patients who were preoperatively diagnosed with right adnexal tumors as in the present cases. Although the prognosis of this disease is generally good, if it develops into PMP, it requires aggressive therapy and may have poor outcomes. When diagnosing tumors in the right adnexal region, it is important for gynecologists to keep this condition in mind and to select the appropriate treatment plan. Minimally invasive surgery may be the preferred option when possible.
The authors have no conflict of interest to be declare.
We obtained informed consent from patients for the publication.
