Discussion

PMP is a rare clinicopathologic syndrome characterized by progressive accumulation and dissemination of mucinous ascites throughout the peritoneal cavity, most commonly originating from an appendiceal mucinous neoplasm [4]. The estimated incidence is approximately two to four cases per million individuals annually, making PMP an uncommon but clinically significant malignancy [5]. Classic symptoms include progressive abdominal distension, abdominal or pelvic pain, early satiety, and gastrointestinal dysfunction secondary to increasing intra-abdominal tumor burden [6]. In contrast to the typically indolent clinical course of PMP, the present case demonstrated rapid progression, radiographic findings concerning for thoracic involvement, and high-grade histopathology, highlighting the substantial heterogeneity that exists within this disease spectrum.

A particularly notable feature of this case was the patient's atypical presenting symptoms, which preceded recognition of the underlying malignancy. Gynecomastia, ejaculatory dysfunction, pelvic pain, and hydrocele formation are not recognized manifestations of PMP and initially directed evaluation toward endocrine and genitourinary etiologies rather than an intra-abdominal neoplasm. Although these symptoms preceded the diagnosis of PMP, a causal relationship cannot be established. Previous reports have described unusual presentations of PMP, including scrotal masses, inguinal hernias, uterine prolapse, and presumed ovarian pathology; however, the constellation of symptoms observed in this patient has not been widely reported [7-10]. The absence of classic abdominal manifestations likely contributed to the delayed diagnosis, which was ultimately established at exploratory laparotomy before transfer to the receiving institution. Similar diagnostic challenges have been described in other reports of PMP presenting with nonspecific or atypical symptoms, underscoring the importance of maintaining a broad differential diagnosis when persistent, unexplained symptoms fail to respond to conventional evaluation [10]. The pathogenesis of PMP remains incompletely understood. Although Helicobacter pylori is a well-established risk factor for certain gastric malignancies [11], microbial factors have also been investigated for their potential role in the biology of PMP, including possible effects on the tumor microenvironment and signaling pathways [12,13]. However, no causal relationship between Helicobacter pylori infection and PMP has been established, and the relevance of these findings to the present case remains uncertain.

Another important aspect of this case was the reported unremarkable abdominal MRI performed in January 2024. According to the outside radiology report, the MRI was interpreted as unremarkable; however, the original MRI images were unavailable for independent review. Repeat CT imaging obtained approximately three months later demonstrated substantial disease burden, including loculated ascites and a large abdominal mass. Although both MRI and CT are used in the evaluation of PMP, CT remains the preferred imaging modality because of its ability to identify mucinous deposits, omental caking, visceral scalloping, and the overall extent of peritoneal involvement [19]. Because the original MRI images were unavailable for independent review, it remains uncertain whether the discrepancy between the reported MRI findings and the subsequent CT reflects early disease, differences in imaging technique or protocol, or variability in radiologic interpretation. Nevertheless, this case underscores the importance of repeat imaging and further evaluation when symptoms progress despite an initially nondiagnostic imaging study.

Histopathologic evaluation confirmed high-grade mucinous adenocarcinoma with signet-ring cells and positive CK7, CK20, CDX2, and SATB2 immunostaining (Figures 5-6). These findings support lower gastrointestinal differentiation but do not establish a specific primary site. Although an appendiceal origin is most commonly associated with PMP, esophagogastroduodenoscopy and colonoscopy performed in November 2024 did not identify a primary gastrointestinal malignancy, and a definitive primary tumor site could not be established based on the available clinical, operative, and pathologic information. Because the complete outside pathology report was unavailable for review, standardized PSOGI classification of the peritoneal disease could not be confirmed. Expression of CDX2 and SATB2 (Figure 5) strongly supports a gastrointestinal, particularly appendiceal or colorectal, origin and is frequently used to characterize mucinous neoplasms associated with PMP [17]. The presence of signet-ring cells is associated with more aggressive tumor biology and poorer prognosis, consistent with this patient's rapidly progressive clinical course. Although long-term survival has been reported following treatment of PMP, particularly among patients with low-grade disease and complete cytoreduction [14], high-grade disease is associated with increased recurrence rates, reduced responsiveness to therapy, and significantly poorer survival outcomes [15,16]. The present case illustrates the aggressive end of the PMP disease spectrum and underscores the prognostic significance of high-grade histology and signet-ring cell morphology.

Radiographic findings concerning for thoracic involvement represented another unusual feature of this case. PMP is generally confined to the peritoneal cavity, and pleural extension has been reported only rarely [18]. Several mechanisms have been proposed to explain thoracic dissemination, including hematogenous spread, lymphatic spread, and transdiaphragmatic migration of mucin-producing tumor cells [18]. Although the imaging findings were concerning for thoracic extension, histologic confirmation was not obtained. Pleural fluid cytology was repeatedly negative for malignant cells, EBUS failed to identify a suitable biopsy target, and pleural biopsy was considered prohibitively high risk. Alternative explanations for the pleural effusions, including severe pneumonia, systemic inflammation, and critical illness, cannot be excluded. Given the patient's extensive ascites and persistent pleural effusions, transdiaphragmatic or lymphatic dissemination appears most plausible. The radiographic thoracic abnormalities and associated pleural effusions substantially complicated management by impairing respiratory mechanics, limiting effective drainage, and contributing to prolonged ventilator dependence. The patient's respiratory status was further complicated by ventilator-associated pneumonia caused by Enterobacter cloacae complex and Serratia marcescens. Collectively, these findings suggest that radiographic thoracic abnormalities in patients with advanced PMP warrant careful evaluation, although the precise etiology of the pleural findings in this patient could not be definitively established.

Obtaining confirmatory tissue and complete histopathologic characterization at the receiving institution proved challenging. The initial diagnosis of PMP had already been established during the exploratory laparotomy performed at the outside institution before transfer, where ascitic-fluid cytology was positive for malignant cells, and an intraoperative biopsy demonstrated mucinous adenocarcinoma. However, the complete outside pathology report was unavailable for review after transfer. Subsequent minimally invasive procedures, including thoracentesis, abdominal fluid drainage, and EBUS-guided sampling, failed to provide adequate tissue for confirmatory histopathologic evaluation and immunophenotypic characterization. Pleural and abdominal fluid samples obtained at the receiving institution were repeatedly negative for malignant cells despite advanced disease. These later negative findings did not negate the previously established diagnosis and likely reflect the recognized sampling limitations of mucinous neoplasms, as mucinous collections are often paucicellular and may yield acellular mucin without representative neoplastic cells [20]. Diagnostic laparoscopy subsequently provided adequate tissue to confirm the previously established diagnosis and to permit comprehensive histopathologic and immunophenotypic characterization of the tumor. This case highlights the importance of obtaining adequate tissue when prior pathology is unavailable for review or when additional histopathologic and immunophenotypic characterization is necessary to guide treatment planning.

CRS-HIPEC remains the accepted standard of care for appropriately selected patients with PMP [21]. This approach has significantly improved long-term survival and disease control compared with historical debulking procedures [22]. In this case, diagnostic laparoscopy demonstrated extensive unresectable peritoneal disease. Additional factors limiting operative candidacy included ventilator-dependent hypoxemic and hypercapnic respiratory failure, declining functional status, severe chronic illness-related malnutrition, radiographic findings concerning for thoracic involvement, and poor overall clinical condition. Nutritional assessment documented greater than 20% estimated weight loss over one year, energy intake below 50% of estimated requirements for more than one month, severe orbital fat depletion, and severe temporal and clavicular muscle wasting. The patient required enteral nutrition via nasogastric tube, which at the time of assessment provided only approximately 36% of estimated caloric requirements and 28% of estimated protein requirements. Although a formal Eastern Cooperative Oncology Group (ECOG) performance status and Peritoneal Cancer Index (PCI) were not documented, these findings, together with unresectable disease and prolonged ventilator dependence, supported the multidisciplinary determination that CRS-HIPEC was not appropriate. Furthermore, evidence suggests that the survival benefit of CRS-HIPEC is reduced in patients with high-grade disease and extra-abdominal extension [15,22,23]. Current peritoneal surface malignancy guidelines generally regard extraperitoneal disease as a major limitation to curative surgical intervention [23]. Following multidisciplinary discussion, the patient received one cycle of palliative FOLFOXIRI; however, no further systemic therapy was administered because of persistent ventilator dependence, progressive clinical deterioration, and subsequent bacteremia requiring vasopressor support. Consequently, this case highlights the narrow therapeutic window that exists in aggressive PMP and emphasizes the importance of early recognition and referral to specialized centers before progression renders definitive treatment infeasible.

Overall, this case illustrates several uncommon features, including atypical endocrine and genitourinary presenting symptoms, initially nondiagnostic imaging, radiographic findings concerning for thoracic involvement, repeated nondiagnostic cytologic studies, and an unusually aggressive clinical course. These findings reinforce the importance of maintaining a broad differential diagnosis, obtaining adequate tissue for histopathologic confirmation when minimally invasive sampling is nondiagnostic, and facilitating early referral to specialized peritoneal surface malignancy centers before disease progression limits potentially curative treatment.

A chronological timeline of the patient's clinical course is presented in Table 1.

Time Point | Event
2023 | Initial presentation with progressive gynecomastia, ejaculatory dysfunction, and pelvic pain.
January 2024 | MRI abdomen/pelvis reported as unremarkable.
April 2024 | CT abdomen/pelvis demonstrated loculated ascites and a large abdominal mass.
June 2024 | Progressive abdominal distension and unintentional weight loss.
November 2024 | Esophagogastroduodenoscopy and colonoscopy performed; no primary gastrointestinal malignancy identified.
February 2025 | Exploratory laparotomy at outside institution established diagnosis of pseudomyxoma peritonei with high-grade mucinous adenocarcinoma; approximately 11 L of malignant ascites evacuated.
Hospital day -3 | CTA chest demonstrated bilateral pleural effusions, mediastinal abnormalities, and findings concerning for thoracic involvement.
Hospital day 1 | Hospitalized with acute hypercapnic respiratory failure requiring endotracheal intubation.
Hospital day 11 | Transferred to Arrowhead Regional Medical Center for evaluation for CRS-HIPEC.
Hospital days 18-23 | Thoracentesis, abdominal drainage, and EBUS performed; cytology and tissue sampling remained nondiagnostic.
Hospital day 30 | Diagnostic laparoscopy confirmed unresectable high-grade mucinous adenocarcinoma with signet-ring cells.
Hospital days 37-39 | One cycle of palliative FOLFOXIRI (5-fluorouracil, leucovorin, oxaliplatin, and irinotecan) administered.
Hospital days 40-54 | No further chemotherapy administered because of persistent ventilator dependence, Enterobacterales and Serratia marcescens bacteremia requiring vasopressor support, and progressive clinical deterioration.
Hospital day 55 | Patient died despite multidisciplinary management.