Low-grade appendiceal mucinous neoplasm with heterotopic ossification and pseudomyxoma peritonei: a case report

Abstract

Introduction:

Heterotopic ossification (HO) within the gastrointestinal tract is extremely rare, and its association with low-grade appendiceal mucinous neoplasm (LAMN) and pseudomyxoma peritonei (PMP) is exceptional. We report a rare case of LAMN with visceral HO and PMP, highlighting its clinical features, pathological findings, and postoperative outcomes.

Case Presentation:

A 55-year-old female presented with progressive abdominal distension over 4 months. Imaging suggested an ovarian mass with ascites. Intraoperatively, gelatinous material filled the peritoneal cavity, with findings consistent with PMP. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, appendectomy, and right hemicolectomy. Histopathology confirmed LAMN with ovarian involvement, dystrophic calcification, and foci of mature ossification within the appendix. The patient declined adjuvant chemotherapy but remained under surveillance. At 12 months follow-up, she remains asymptomatic with no radiological evidence of recurrence.

Discussion:

Visceral HO is an uncommon phenomenon, possibly involving epithelial–mesenchymal transition (EMT) and bone morphogenetic protein pathways. While EMT is theoretically linked to aggressive tumor biology, the clinical course in this case has been indolent.

Conclusion:

The coexistence of LAMN, PMP, and HO underscores the complex biology of mucinous appendiceal tumors. While HO represents a rare pathological differentiation, long-term surveillance is required to determine its true prognostic significance.

Introduction

Heterotopic ossification (HO) is the abnormal formation of mature bone within nonskeletal tissues. It is typically associated with trauma, burns, neurologic injury, or genetic disorders such as fibrodysplasia ossificans progressiva, but it has also been reported in association with neoplastic processes, particularly mucinous tumors of the gastrointestinal tract^[1,2].

HIGHLIGHTS

• We present a rare case of low-grade appendiceal mucinous neoplasm (LAMN) with pseudomyxoma peritonei (PMP) and heterotopic ossification (HO).

• Visceral HO in association with mucinous appendiceal tumors is exceptionally uncommon, with very few cases reported.

• Histopathology revealed dystrophic calcification and mature bone formation within the appendix alongside PMP.

• This case underscores the importance of recognizing HO in mucinous tumors, as it may reflect aggressive biology and influence prognosis.

Pseudomyxoma peritonei (PMP), often referred to as “jelly belly,” is characterized by progressive accumulation of mucinous ascites due to dissemination of mucin-producing tumors, most commonly low-grade appendiceal mucinous neoplasms (LAMNs). The condition is rare, with an estimated incidence of less than four cases per million per year and a female predominance^[3,4].

HO occurring in the setting of appendiceal neoplasms and PMP is exceptionally rare, with only a few cases reported in the literature^[5–7]. We present a case of LAMN with associated HO and PMP in a 55-year-old woman, highlighting its clinical, histopathological, and therapeutic implications.

Case presentation

A 55-year-old Ethiopian para IX woman presented with a 4-month history of progressive abdominal swelling and dull aching abdominal pain. She had been amenorrheic for 8 years, with one episode of postmenopausal bleeding 2 months prior. There was no history of bowel habit changes, weight loss, systemic illness, or previous abdominal surgery.

On examination, her vital signs were stable. A large, soft, nontender abdominopelvic mass with positive fluid thrill was noted. Pelvic examination revealed a smooth cervix with no masses or discharge. Laboratory investigations, including complete blood count, liver and renal function tests, serum electrolytes, and CA-125, were within normal limits. Chest X-ray was unremarkable. Ultrasound showed a large complex cystic abdominopelvic mass with septations and mural nodules, suggestive of an ovarian tumor. CT scan was unavailable.

With a provisional diagnosis of an ovarian tumor, exploratory laparotomy was performed. Intra-operatively, abundant gelatinous material was found filling the peritoneal cavity (Fig. 1). The uterus and ovaries appeared grossly normal. Surgical procedures included total abdominal hysterectomy, bilateral salpingo-oophorectomy, right hemicolectomy, and omentectomy.

Figure 1.

Intraoperative image showing a jelly material that has filled the abdominal cavity.

Histopathological examination of the appendix revealed mucinous epithelium with villous projections lined by bland columnar cells exhibiting mild to moderate atypia, pseudo-stratification, and extracellular mucin with pushing margins. Foci of dystrophic calcification and mature trabecular bone formation consistent with HO were present in the submucosa (Figs. 2 and 3). Omental and ovarian tissues showed mucin pools containing scattered mildly atypical columnar cells, consistent with PMP.

Figure 2.

Villous epithelial proliferation with obliterated submucosal space (lower left) and a focus of ossification and dystrophic calcification with well-formed trabecular bone (upper right).

Figure 3.

A close-up view of the ossified focus showing mature bone with osteocytes in their lacunar spaces.

Postoperative recovery was uneventful, and the patient was discharged on postoperative day 7. She was referred to oncology for adjuvant therapy (Hyperthermic Intraperitoneal Chemotherapy was unavailable) but declined systemic chemotherapy. The patient was placed on a surveillance protocol with visits conducted at 3, 6, and 12 months. At the 12-month follow-up, the patient remains alive and asymptomatic. Repeat abdominal ultrasound showed no re-accumulation of ascites, and serum tumor markers remained normal.

Discussion

HO is most commonly associated with trauma, burns, orthopedic procedures, and neurologic injury, where local inflammation and tissue injury initiate an osteogenic cascade^[1,2]. In contrast, HO occurring within visceral organs or associated with neoplasms is exceedingly rare. When present in tumors, it is believed to result from aberrant activation of osteogenic pathways within the tumor microenvironment. Experimental and morphologic studies suggest that bone morphogenetic proteins (BMPs) released by tumor cells or stromal elements can drive mesenchymal precursor cells toward osteoblast differentiation^[8]. In addition, a partial epithelial–mesenchymal transition (EMT) may enable neoplastic epithelial cells to acquire mesenchymal features, secrete BMPs, or act as osteogenic progenitors themselves, thereby facilitating ectopic bone formation^[9].

Among epithelial malignancies, mucinous neoplasms of the colon and appendix are the most frequently reported in association with HO. Their abundant extracellular mucin, chronic inflammatory milieu, and hypoxic microenvironment may further promote osteogenic signaling and maturation of osteoid tissue^[6,7]. Despite this predisposition, HO remains an exceptionally uncommon finding in appendiceal tumors. Only a small number of cases involving appendiceal mucinous neoplasms with HO have been published to date^[5–7], underscoring the rarity of this phenomenon and highlighting the value of the present case in expanding the available literature.

PMP is classified histologically by the Peritoneal Surface Oncology Group International into acellular mucin, low-grade mucinous carcinoma peritonei (disseminated peritoneal adenomucinosis), high-grade mucinous carcinoma peritonei, and high-grade disease with signet-ring cells, with prognosis worsening across grades^[10]. Our patient’s findings were consistent with low-grade disease.

Clinically, PMP presents with nonspecific abdominal symptoms or increasing abdominal girth. CT imaging is the gold standard for diagnosis, showing loculated mucinous ascites and peritoneal nodules^[11]. Optimal treatment includes cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), which improves survival compared to surgery alone^[12,13]. In our case, resource limitations precluded HIPEC, and the patient declined adjuvant therapy.

The presence of HO involves EMT, a process often linked to tumor invasiveness and resistance to therapy^[9]. Consequently, it has been hypothesized that osseous metaplasia might portend a more aggressive biological behavior. However, clinical outcomes reported in the literature are variable. In the present case, despite the theoretical risk associated with EMT and the lack of adjuvant therapy, the patient has maintained a disease-free status for 12 months. This suggests that while HO indicates a complex tumor microenvironment, it does not necessarily override the generally indolent prognosis of low-grade appendiceal neoplasms when adequate surgical cytoreduction is achieved. The “aggressive” biology suggested by the presence of bone formation was not clinically evident in this patient’s postoperative course.

Conclusion

This case highlights a rare coexistence of LAMN with PMP and heterotopic ossification. While the presence of bone formation implies mesenchymal differentiation potential within the tumor, this case demonstrates that such findings do not invariably lead to rapid recurrence or poor short-term survival. Continued long-term surveillance is essential to fully understand the prognostic implications of this rare pathological entity.

SCARE guidelines

This work has been reported in accordance with the SCARE criteria (Surgical Case Report Guidelines)^[14].

Ethical approval

Ethical approval was obtained for the publication of this case report.

Consent

Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the consent is available upon request.

Sources of funding

No funding was received for this case report.

Author contributions

S.A.A.: Writing – original draft, Data curation, Conceptualization, Resources; S.A.B.: Writing – review and editing, Resources, Supervision. Y.D.M.: Writing – review and editing, Resources, Supervision; E.T.Y.: Writing – original draft, Data curation, Conceptualization; M.B.H.: Writing – review and editing, Resources; M.A.W.: Writing – review and editing, Resources.

Conflicts of interest disclosure

The authors declare no competing financial interests or personal relationships that could influence this work.

Research registration unique identification number (UIN)

Not applicable.

Guarantor

Dr. Suleiman Ayalew Belay.

Data availability statement

All data supporting the findings of this case report are included within the manuscript. No additional datasets were generated or analyzed.

Acknowledgements

Not applicable.