Appendiceal endosalpingiosis: a case report and review of the literature.

A 21-year-old Iranian woman presented to emergency department with 2 days of severe abdominal pain. The pain started in the right lower quadrant of the abdomen and became sharp and constant in 2 days, with no migration, radiation, or relief. The symptom was associated with subjective fever; however, at the presentation, her body temperature was 37.3 °C. The patient also complained of nausea and anorexia but no vomiting. There were no symptoms of bowel, vaginal, or urinary complaints reported. The patient was in the 21st day of her regular menstruation cycle and had had no sexual activity in the past 2 months. Before presentation, the patient had been well, with no significant past medical history and had had no similar complication. The patient’s surgical history included a rhinoplasty 2 years ago. Upon presentation, physical examination revealed a stable patient, with severe tenderness of the right lower quadrant of the abdomen and no rebound tenderness, in addition to right iliac fossa pain, particularly around McBurney’s point. Rosving’s, obturator, and psoas signs were negative. Pain with percussion was also negative. Moreover, per vaginal examination, there were also no abnormalities. The white cell count (WBC) was 7.4 × 1000/mm 3 with 58.1% neutrophils. She also had C-reactive protein (CRP) of 3.6 mg/L, creatinine of 1 mg/dL, negative beta-human chorionic gonadotropin (B-HCG), and normal urine analysis (Table  1 ). The computed tomography (CT) reported enlarged appendix (Fig.  1 ). Table 1 Laboratory test results Test, unit Result Reference range WBC, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\times$$\end{document} × 1000/mm 3 7.4 4.0–10 RBC, million/mm 3 4.48 4.5–6.3 Hb, g/dL 12.8 12–16 Hematocrit, % 40.6 30–45 MCV, fL 90.6 77–97 MCH, Pgm 28.6 27–32 MCHC, % 31.5 32–36 Platelet, × 1000/mm 3 248 140–440 Neutrophil, % 41.9 — Lymphocyte, % 58.1 CRP, mg/L 3.6 Positive: > 6 Na, mEq/L 142 136–145 K, mEq/L 4.4 3.7–5.5 BUN, mg/dL 6 5–23 Creatinine, mg/dL 1.0 0.5–1.5 Urine analysis  Color Yellow —  Appearance Clear —  pH 7 —  Specific gravity 1.005 —  Protein Negative —  Blood Negative —  Hb Negative —  Glucose Negative —  Nitrite Negative —  Ketone Negative —  WBC 0–1 —  RBC 0–1 —  Epithelial cell 1–2 —  Crystal Negative —  Cast Negative — WBC white blood cell, RBC red blood cell, Hb hemoglobin, MCV mean corpuscular volume, MCH mean corpuscular hemoglobin, MCHC mean corpuscular hemoglobin concentration, CRP C-reactive protein, Na sodium, K potassium, BUN blood urea nitrogen Fig. 1 Abdominal computed tomography scan without contrast; the arrow shows the enlarged appendix Laboratory test results WBC white blood cell, RBC red blood cell, Hb hemoglobin, MCV mean corpuscular volume, MCH mean corpuscular hemoglobin, MCHC mean corpuscular hemoglobin concentration, CRP C-reactive protein, Na sodium, K potassium, BUN blood urea nitrogen Abdominal computed tomography scan without contrast; the arrow shows the enlarged appendix The patient was admitted, and according to possible diagnosis of acute appendicitis, antibiotic therapy with ceftriaxone (1 g intravenously three times daily) and metronidazole (500 mg intravenously three times daily) were started. As her abdominal symptoms continued with no relief, the patient was transferred to the operating room for laparoscopic appendectomy. The patient had a macroscopic thickened appendix without other abnormalities, and the specimen was sent for further histological evaluation (Fig.  2 ). The pain was subsequently relieved, and the patient was discharged without any complications. Macroscopically, the serosal surface of the specimen was gray and rough, covered with fibrinopurulent exudate. Cut sections showed a dilated lumen filled with pus (Fig.  2 ). Histopathology showed no evidence of malignancy, with moderate to severe mucosal appendicitis; in addition, in hematoxylin and eosin (H&E) staining there was one cyst located in muscular and serosal layers of the appendix, which was lined by bland-looking ciliated columnar epithelium (fallopian-tube-like) (Fig.  3 ). During her follow-ups, the patient was assessed for any gynecological abnormalities; however, all results were negative. Fig. 2 Macroscopic thickened appendix after the laparoscopic appendectomy Fig. 3 Histopathology of appendix with hematoxylin and eosin staining; there is one cyst located in the muscular and serosal layers of appendix ( A ), which is lined by bland-looking ciliated epithelial cells ( B ) Macroscopic thickened appendix after the laparoscopic appendectomy Histopathology of appendix with hematoxylin and eosin staining; there is one cyst located in the muscular and serosal layers of appendix ( A ), which is lined by bland-looking ciliated epithelial cells ( B )

Pelvic endosalpingiosis was first described by Sampson in 1930 [ 12 ]; it is a rare benign condition in which ciliated tubal epithelium similar to that of the fallopian tubes’ deposits are found along serosal surfaces in the pelvis. It is hypothesized that inflammation or chronic damage to the tubes may lead to proliferation of these cells, which then deposit along serosal surfaces in a manner similar to endometriosis [ 13 , 14 ]. Another hypothesis for the development of endosalpingiosis involves a multicentric metaplastic process (coelomic metaplasia) known as mesothelial metaplasia, which may be hormonally influenced [ 15 ]. The reported prevalence of endosalpingiosis in the literature ranges from 1% to 22% [ 16 – 18 ], based on pathological analyses of various populations of women undergoing gynecological surgery. In a retrospective study of 13 patients, 5 were asymptomatic, 5 had abdominal or pelvic pain, but only 4 had the same pain and disease location [ 19 ]. The patient also presented with a history of increasing right lower quadrant pain and tenderness, coincident with the place of endosalpingiosis. Incidentally diagnosed, the disease is associated with both benign and malignant gynecological conditions, such as endometriosis [ 20 ]. Histopathologically, endosalpingiosis is distinguished from endometriosis by the presence of ciliated glandular epithelium, the absence of stromal component of endometrium, and the lack of inflammatory response. Importantly, endometriosis has been reported concurrently in one third of cases [ 16 , 17 ]. Pelvic endosalpingiosis has been found histologically in lymph nodes and ovaries, with serosal implants along the colon, bladder, and uterus. Cases involving the appendix are rarely reported [ 16 , 21 ]. Appendiceal endosalpingiosis is a rare entity. Cajigas et al . presented the first case of appendiceal endosalpingiosis with abdominal pain, fever, and vaginal bleeding in 1991 [ 7 ]. On clinical examination, diffuse tenderness and guarding were observed, and laboratory tests revealed mild leukocytosis. Regarding possible acute appendicitis, the patient underwent an appendectomy; however, although there were no signs of acute appendicitis, a thickened focal serosal surface was observed on the appendix [ 7 ]. Since then, only six cases have been reported; these are summarized in Table  2 [ 1 , 3 , 8 – 11 ]. Tudor et al . described two similar cases with patients presenting with right lower quadrant pain but white blood cell (WBC) counts within normal range. Authors also found a low-density cystic mass in the tip of the appendix of both patients via contrast-enhanced multidetector CT. In contrast, our patient did not show any abnormalities in the abdominopelvic CT scan, only appendix enlargement. It is noteworthy that, as the patients did not provide consent on contrast imaging, the results could not be as detailed as per Tudor et al . Moreover, Pollheimer and colleagues described a case of acute abdominal pain and complications related to diverticulitis. In this patient, a laparotomy was performed, and a polycystic tumor measuring 0.8 cm was observed in the appendix. Following the examinations conducted, the final diagnosis of appendiceal endosalpingiosis was established [ 22 ]. Demir et al . also discussed the imaging characteristics, differential diagnosis, and clinical significance of appendiceal endosalpingiosis, emphasizing that accurate diagnosis of this condition could lead to better management of patients’ cases [ 8 ]. Consistent with our report, Nayak et al . presented a case of abdominal pain, fever, and anorexia. Imaging studies revealed a thickened appendix. The patient underwent laparoscopic appendectomy, and the pathological examinations confirmed the diagnosis of appendiceal endosalpingiosis [ 10 ]. While our case of appendiceal endosalpingiosis and that with the reported signet ring cell carcinoma [ 23 ] both presented as appendicitis mimics, they represent biologically and clinically distinct entities. The critical differences are as follows: Histopathologically, our specimen showed benign ciliated tubal-type epithelium (Fig.  3 ) without the mucin-filled signet ring cells or nuclear atypia characteristic of carcinomas. Clinically, our patient achieved complete resolution with simple appendectomy and required only gynecological surveillance, in contrast to the aggressive multimodal therapy needed for signet ring cell carcinoma. Prognostically, endosalpingiosis has no malignant potential, while signet ring cell carcinoma shows 82% mortality at 5 years. These distinctions confirm that appendiceal endosalpingiosis represents a separate diagnostic category requiring unique clinical consideration [ 23 ]. Table 2 Summary of previous cases of appendiceal endosalpingiosis Reference Country Year Age (years) Presenting signs and symptoms PMH Imaging Management Pathology report Gynecological assessment Cajigas et al . [ 7 ] USA 1990 40 Fever, abdominal pain and tenderness with right-sided guarding, vaginal bleeding Unremarkable No imaging Right salpingo-oophorectomy and laparoscopic appendectomy Hydrosalpinx with transmural necrotizing salpingitis, endosalpingiosis within the muscularis propria of the appendix, cystic trabeculated focus 0.5 × 0.5 cm, no acute appendicitis observed Right tubo-ovarian abscess found via laparoscopic exploration Pollheimer et al . [ 11 ] Austria 2006 82 Acute abdominal pain due to perforated sigmoid diverticular disease, with subsequent purulent pelvic peritonitis Not specified No imaging Laparotomy with excision of diseased colonic segment, on-table lavage, appendectomy Cystic tumor at the tip of the appendix, lined by tubal-type epithelium with ciliated and secretory cells. Immunohistochemistry: positive for pancytokeratin, EMA, CK7, ER; negative for CK20,CD10, mesothelial markers, MUC2 Not specified Aguilar et al . [ 9 ] Spain 2009 36 Sudden hypogastric abdominal pain for 4 h, fever, nausea, vomiting, peritoneal irritation signs (intense in hypogastrium), leukocytosis, pyuria Childhood hepatitis A Ultrasound: normal uterus and adnexa, free fluid in the Douglas pouch, right iliac fossa, and vesicouterine pouch Emergency laparoscopy, prophylactic appendectomy, right ovarian cystectomy Focal endosalpingiosis in the appendix tip, cystic ovarian endometriosis Further follow-up suggested Demir et al . [ 8 ] Türkiye 2017 30 Abdominal pain and classical signs of appendicitis Not specified CT scan: cystic endosalpingiosis along with appendicolith in the middle part of the inflamed and enlarged appendix Not specified Cystic appendiceal endosalpingiosis Not specified Tudor et al . [ 3 ] USA 2019 41 Right lower quadrant pain (8/10) for 2 days Tubal ligation CT scan: 18 mm eccentric cystic mass at the tip of the appendix with minimal/no inflammatory response Laparoscopic appendectomy Cystic appendiceal endosalpingiosis Not specified 36 Increasing right lower quadrant pain over 4 days (similar to prior pain from previous appendectomy) 1: Prior laparoscopic appendectomy 2: Partial hysterectomy 3: Endometriosis CT scan: 19 × 23 mm rim-enhancing eccentric cystic mass at the tip of the appendiceal stump, along the suture margin Open laparotomy due to previous appendectomy Cystic appendiceal endosalpingiosis Not specified Nayak et al . [ 10 ] Australia 2022 56 7 days of sharp and constant abdominal pain, initially dull and peri-umbilical, which migrated to the right iliac fossa; subjective fevers; anorexia 1: Postmenopausal 2: Two lower segment cesarean sections CT scan: Thickened appendix (11 mm), consistent with acute appendicitis. No significant fat stranding, intraperitoneal free fluid, or gas Laparoscopic appendectomy Mild acute mucosal appendicitis with endometrial-type glands (no stroma, no hemosiderin-laden macrophages), consistent with endosalpingiosis. No malignancy Not specified Sealey et al . [ 1 ] Australia 2024 40 Abdominal pain (initially dull in right upper quadrant, later severe and migrating to lower abdomen), similar to previous menstrual pain 1: Severe menorrhagia and dysmenorrhea 2: Endometrial ablation 3: Transvaginal total hysterectomy CT scan: 14 mm appendix with significant surrounding fat stranding, small volume of free fluid, no free gas or organized collection Laparoscopic appendectomy Gangrenous acute appendicitis, occasional glands lined by ciliated, flattened to columnar cells (consistent with endosalpingiosis), no evidence of epithelial dysplasia or neoplasia Suggested for further follow-up Ina et al . [ 23 ] USA 2024 77 Right lower quadrant pain (5 days), abdominal distension, no fever/vomiting HTN, DM, hyperthyroidism CT/MRI: Dilated appendix, peritoneal thickening, omental nodularity, ascites, liver lesion Exploratory laparoscopy, biopsy, palliative care, chemotherapy required Signet ring cells with mucin, peritoneal carcinomatosis (malignant), ovarian metastasis suspected Ovarian involvement suspected (metastasis) Current case Iran 2024 21 Severe right lower quadrant abdominal pain (2 days), nausea, subjective fever, anorexia 1: Rhinoplasty 2 years ago 2: No gynecological history CT scan: enlarged appendix only, with no metastatic signs Diagnostic laparoscopy, simple appendectomy, rapid discharge Moderate to severe mucosal appendicitis, cyst lined by ciliated columnar epithelium (fallopian tube-like) in the appendix, no malignant cells Benign condition, excellent prognosis, no metastasis DM, diabetes mellitus; HTN, hypertension; PMH, past medical history Summary of previous cases of appendiceal endosalpingiosis USA 1990 Austria 2006 Spain 2009 Türkiye 2017 USA 2019 1: Prior laparoscopic appendectomy 2: Partial hysterectomy 3: Endometriosis Australia 2022 1: Postmenopausal 2: Two lower segment cesarean sections Australia 2024 1: Severe menorrhagia and dysmenorrhea 2: Endometrial ablation 3: Transvaginal total hysterectomy USA 2024 Iran 2024 1: Rhinoplasty 2 years ago 2: No gynecological history DM, diabetes mellitus; HTN, hypertension; PMH, past medical history Unlike aggressive malignancies such as signet ring cell carcinoma, endosalpingiosis is a benign condition with no reported cases of malignant transformation. However, its association with gynecological cancers warrants attention. Another significant association reported with pelvic endosalpingiosis is an increased risk of female malignancies, particularly serous ovarian tumors with low malignant potential, or so-called serous borderline ovarian tumors (SBOT). To a lesser extent, it is also associated with ovarian cystadenocarcinoma [ 13 , 15 , 24 ]. Endosalpingiosis has been associated with ovarian and uterine cancers. Hermens et al . reviewed 2500 cases of histologically confirmed endosalpingiosis in women from 1990 to 2015 and found an age-adjusted incidence ratio of 43.7 (95% CI 35.1–54.3) for ovarian cancer [ 20 ]. Authors also observed that this association was stronger with serous and endometrioid subtypes of ovarian cancer and was independent of concurrent endometriosis diagnosis. On the basis of subgroup analysis, they found that the association was primarily due to cases where endosalpingiosis and ovarian cancer were diagnosed, particularly when one was diagnosed 6 months prior to the other. Through a large study, Esselen et al . found a significant association between endosalpingiosis and ovarian, fallopian tube, primary peritoneal, and uterine cancers. They found that the association was strongest with serous borderline ovarian tumors [ 16 ]. In our case, we referred the patient to a gynecologist, and all the tests were negative for malignancies or any other abnormalities in relation to genital system. According to the absence of such assessments in previous cases, we suggest that this evaluation becomes a routine in patients with appendiceal endosalpangiosis. To date, none of the reported cases of appendiceal endosalpingiosis have resulted in ovarian malignancy [ 3 ]. Nevertheless, to our knowledge there are no longitudinal prospective studies on patients presenting with endosalpingiosis evaluating the odds of future cancers, and associated risk factors. Given the relative rarity of endosalpingiosis, particularly appendiceal endosalpingiosis, recommendations for cancer surveillance after the diagnosis are still under discussion.

In this study, we presented a rare case of appendiceal endosalpingiosis mimicking acute appendicitis. The information regarding the potential association between appendiceal endosalpingiosis and gynecologic cancers is limited. It remains unclear whether further research or closer monitoring is needed for the early detection of uterine or ovarian cancers in these patients. Surgeons should always be aware of the pathologic evaluation of surgical site biopsy to make the best choice during follow-ups regarding varied differential diagnosis. Further research is necessary to better understand the connection between appendiceal endosalpingiosis and gynecologic cancers. Such studies could enhance patient diagnosis and management, additionally, helping prevent potential complications associated with this condition.

Endosalpingiosis is a benign and rare histopathological diagnosis characterized by the ectopic presence of glandular tissue consisting of benign ciliated tubal epithelium (considered part of the spectrum of peritoneal serous lesions) outside the fallopian tubes [ 1 , 2 ]. As the diagnosis is made only through biopsy, the exact incidence is hard to determine; nevertheless, a prospective analysis on 1107 women undergoing laparoscopy revealed that 7.6% had evidence of endosalpingiosis, of which 40% were postmenopausal and 34% had concomitant endometriosis [ 3 ]. This rare phenomenon is also more frequently seen in women with previous gynecological manipulation. It is commonly found in the ovary, fallopian tube, omentum, and uterus; recently there also have been reports of skin, spinal nerve root attachment, and axillary lymph node involvement [ 4 – 7 ]. Endosalpingiosis is rarely observed in the appendix but may be mistaken for acute appendicitis. There are only seven reports of appendiceal endosalpingiosis, four of which are in the pathology literature, two of which presented with acute appendicitis, and one of which was the cause of appendix perforation [ 1 , 3 , 7 – 11 ]. In the following case, we present the eighth report of this rare disease, in this case in a 21-year-old woman with pain and tenderness in the right lower quadrant of the abdomen, mimicking appendicitis, with no previous medical history, particularly gynecological history. We also discuss the clinical importance, and potential management strategies.