Introduction

Pseudomyxoma peritonei (PMP) is a clinical syndrome characterized by progressive accumulation of mucinous tumor throughout the peritoneal cavity [1, 2]. The median age of patients affected by PMP is about 53 years with a predilection in females (2-3 more frequent); the incidence is approximately 0.2 per 100.000 population per year and develops in about 20% of patients with mucinous appendiceal neoplasms (MANs), but in some cases, it can also be present in patient affected by non-mucinous appendiceal adenocarcinoma (i.e. colon, ovary, and gallbladder) [3]. PMP has an indolent behavior, with a long natural history, and it grows undisturbed until the slow accumulation of mucin within the abdominal cavity leading to dyspnea or bowel obstruction, till eventually, death [4]. Elevated Ca 19.9 and Ca 125 levels can also be present [5, 6]. PMP has in general a poor prognosis, that can be improved to a 5-year overall survival (23–82%) thanks to an integrative therapeutic scheme, termed cytoreductive surgery—hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) [7].

Case presentation

A 58-year-old man was referred to the emergency department for the onset of epigastric pain associated with vomiting intermingled with blood and inappetence in the past 5 days. The patient had in his medical history a chronic HCV-related hepatopathy, treated with antivirals (Glecaprevir and Pibrentasvir), type 2 diabetes mellitus, drugs addiction and appendicular mucocele. Blood tests performed demonstrated a mild leukocytosis (12.20 × 10^9/L), a mild anemia (Hb 12.8 g/dL), transaminase and cholestatic index values at upper limits. The emergency department clinician, therefore, requested an ultrasound (US) of the abdomen; given the patient's unexplorability due to intense intestinal meteorism and the patient's poor clinical condition, further investigation with contrast-enhanced CT (CECT) was immediately required. CECT examination documented an increased size of the liver, with finely irregular margins due to the known sclerogenic liver disease, and a transient hepatic attenuation difference (THAD) in the II hepatic segment. Moreover, CECT showed a voluminous neoformation with lobulated margins and an overwatered density occupying all supra-mesocolic and sub-mesocolic recesses leading to multiple incisions of liver and the spleen. A conspicuous layer of ascitic effusion was also documented.

The appendix showed increased caliber (about 4 cm) with a coprolite near its origin (Fig. 1a,b).

Fig. 1
figure 1

a CECT documents a voluminous mass with lobulated margins occupying the entire peritoneum; b in the right iliac fossa, there is a coprolite in the context of an appendix increased in caliber

Full size image

The image findings supported the hypothesis of PMP. In consideration of CECT findings and patient's medical history, further investigations were made. The oncologic markers Ca 19.9 and Ca 125 were indeed increased, respectively, 745 U/mL (range 0.0–39.0 U/mL) and 196 U/mL (range 0.0–35.0 U/mL). An exploratory laparoscopy with biopsy sampling of two peritoneal nodules and peritoneal fluid was performed. At the exploration, the peritoneal cavity was occupied by abundant ascitic fluid mixed with mucinous micelles. There was massive parietal and visceral peritoneal involvement of all abdominal quadrants; the involved loops of small bowel were agglomerated in the center and indissociable from the neoformation. Histological examination confirmed the presence of high-grade mucinous carcinoma peritonei. Because of the multiple comorbidities, the patient did not undergo to a cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). However, systemic chemotherapy was started with oxaliplatin plus 5-fluorouracil scheme. About 18 months later, the patient died.

Discussion

PMP is a rare and poorly understood disease characterized by disseminated mucinous ascites and peritoneal, serosal, and omental mucinous implants [8]. As in most reports described in the literature, also in our case, a mucinous neoplasm of the appendix (MAN) was the trigger for the onset of PMP [9]. PMP is difficult to diagnose clinically; hence, imaging, particularly CECT, is crucial for a correct diagnosis and to assess the extent of the disease. On CECT typical findings are the presence of low attenuation masses (< 20 HU) scattered throughout the peritoneum with central displacement of the bowel loops. Other typical findings are prominent implants that cause a massive effect on the liver and the spleen producing the typical “scalloping” effect; the diaphragm can be thickened due to the implants of PMP in this site. Implants can present curvilinear peripheral calcifications. Sometimes PMP can metastasize to the ovary, so nodules at that level should not necessarily be considered as primary lesion. PMP only rarely tends to spread to the lymph nodes or directly to the thoracic cavity [6]. All these findings except linear calcifications were in line with our case. Over time, there have been various classification systems aimed to histologically characterize both the appendicular neoplasm, if present, and the degree of cellular atypia found in PMP. In 2016, the Peritoneal Surface Oncology Group International (PSOGI) developed a classification system aimed at grading epithelial neoplasms of the appendix [10]. The nomenclature is as follows:

  1. o

    Low-grade appendiceal mucinous neoplasm (LAMN) extends beyond the mucosa into the appendiceal wall, without infiltrative invasion; it has a low-grade cytologic atypia.

  2. o

    High-grade appendiceal mucinous neoplasm (HAMN) extends beyond the mucosa into the appendiceal wall, without infiltrative invasion; it has a high-grade cytologic atypia.

  3. o

    Mucinous adenocarcinoma shows an infiltrative invasion; it can be well, moderately, or poorly differentiated.

  4. o

    Poorly differentiated mucinous adenocarcinoma with signet ring features.

Although this classification system has a role in the prognostic definition of MANs and the likelihood of developing PMP is lower in poorly differentiated forms, the PSOGI system recommends that PMP be histologically classified based on peritoneal pathology rather than primary neoplasm. The nomenclature is as follows:

  1. o

    Acellular mucin: absence of neoplastic epithelial cells within the peritoneal mucin.

  2. o

    Low-grade mucinous carcinoma peritonei—G1, previously referred to as disseminated peritoneal adenomucinosis (DPAM).

  3. o

    High-grade mucinous carcinoma peritonei—G2, previously referred to as peritoneal mucinous carcinomatosis (PMCA).

  4. o

    High-grade mucinous carcinoma peritonei with signet ring cells—G3, previously referred to peritoneal mucinous carcinomatosis with signet ring cells (PMCA - S) [10].

Cytoreductive surgery (CRS) in combination with (HIPEC) is the foundations of treatment of PMP [11]. Cytoreduction combines multiple peritonectomies—parietal, diaphragmatic and pelvic—and visceral resections—gastrointestinal, hysterectomy and splenectomy—with the “electro evaporation” of unresectable nodules [12]; the goal is to achieve a complete cytoreduction in the absence of macroscopically visible lesions. HIPEC is performed after the completion of surgery; most centers use Oxaliplatin–Mitomycin C chemotherapy in a temperature range of 41.5–43 °C with a perfusion time from 30 to 90 min [12]. Being a highly demolitive treatment, preliminary evaluation (either laparoscopic or CECT) of the extent of the disease is necessary. In this regard, in 1995, Sugarbaker quantified the dispersion of abdominal disease through numerical values correlated to quadrants of the abdomen, determining the peritoneal carcinomatosis index (PCI) [13]. The cytoreductive surgery (CCP) can be classified with the following score:

  1. o

    CC0: no residual tumor.

  2. o

    CC1: residual tumor < 2.5 mm.

  3. o

    CC2: residual tumor 2.6 mm to 2.5 cm.

  4. o

    CC3: residual tumor > 2.5 cm.

The aim of CCP is to achieve a CC0–CC1 score, which can be considered a complete cytoreduction that gives the patient a good prognosis compared with patients with a CC2–CC3 [14]. An intraoperative PCI > 20 is considered a large disease burden and a relative contraindication to CRS as the potential risks are thought to outweigh benefits [15], although some studies affirm that even in the presence of a PCI > 20, low-grade lesions can still be treated with CRS-HIPEC with an acceptable long-term outcome [16]. These observations are in line with the reported case, which indeed had a PCI > 20, a high-grade appendiceal lesion, and multiple comorbidities (diabetes mellitus, HCV-related chronic hepatopathy, and drug addiction). Therefore, our patient was initiated on palliative systemic chemotherapy with oxaliplatin plus 5-fluorouracil scheme. Many studies have documented a fair degree of chemoresistance, either due to the low degree of cell proliferation or the mucin-rich microenvironment that limits the availability of the drugs [17], and thus a worse prognosis than patients who can benefit from CRS-HIPEC.

Conclusion

PMP is a rare disease generally associated to MANs. On CECT, the suspicion of PMP can be proposed if there are clinical and anamnestic data to support the diagnosis. HIPEC-CRS is the gold standard of treatment; but in view its rarity and prognosis, a multidisciplinary approach is always necessary to ensure the best therapeutic outcome.