Navigating Fertility Preservation in Epithelioid Peritoneal Mesothelioma: A Case Study

Introduction

Malignant peritoneal mesothelioma (MPM) is a rare but aggressive neoplasm arising from the serosal membranes lining the peritoneal cavity. Although it accounts for only a small percentage of all mesothelioma cases, MPM’s clinical and pathological challenges make it a formidable disease with significant morbidity and mortality [1,2]. The incidence of MPM has shown a relatively stable trend, with a higher prevalence noted in females, contrasting with the male predominance observed in pleural mesothelioma [3,4]. The etiological role of asbestos exposure, although well-established in pleural mesothelioma, appears to be less pronounced in peritoneal cases, suggesting a multifactorial pathogenesis, including genetic predispositions such as BAP1 mutations [1,5].

The clinical presentation of MPM is often insidious and non-specific, leading to frequent delays in diagnosis. Symptoms such as abdominal distension, pain, and ascites are common but are not unique to this malignancy, often resulting in late-stage detection. Diagnostic modalities such as computed tomography (CT) and magnetic resonance imaging (MRI) are useful for identifying suspicious lesions, yet they lack specificity, necessitating histopathological confirmation through biopsy [2]. The advent of immunohistochemistry (IHC) has greatly enhanced the diagnostic accuracy of MPM, particularly in distinguishing it from other malignancies that present with similar clinical features [6,7]. However, despite advances in diagnostic techniques and therapeutic approaches, including CRS and HIPEC, the prognosis for patients with MPM remains poor, underscoring the need for ongoing research and development of more effective treatment strategies [8,9]. Therefore, an increasing number of studies have focused on the immunotherapies used in mesothelioma, with growing utilization and attention to the treatment outcomes of immune-checkpoint inhibitors (Table 1).

Case Report

INCIDENTAL DISCOVERY OF MALIGNANT PERITONEAL MESOTHELIOMA:

A 44-year-old asymptomatic nulliparous woman presented with a palpable pelvic mass. The physical examination revealed an enlarged uterus of about 10- to 12-week size, which was mobile, firm in consistency, with no uterine or forniceal tenderness, and mild swelling in the right pubic area. The primary diagnosis is an anterior wall uterine leiomyoma, measuring 112×94×108 mm, accompanied by ascites measuring 65×42 mm and a 20×14 mm mass, as identified via gynecological sonography on January 30, 2010. During a laparotomic myomectomy performed on February 17, 2020, an incidental discovery of a pelvic tumor was made.

This tumor appeared as a cauliflower-like lesion disseminated across the right pelvic wall, cul-de-sac, anterior uterine surface, bladder, and colon (Figure 1). A biopsy of the sigmoid colon serosa yielded a 0.8 cm sample, which pathologically demonstrated proliferative mesothelial cells without significant atypia or necrosis. A post-myomectomy CT scan (Figure 2) revealed seeding in the lower pelvis, characterized by multiple small, heterogeneous, enhancing nodules on the peritoneum and a prominent soft-tissue mass in the right adnexa.

Histopathological examination identified bland mesothelial cells and no invasions (Figure 3A–3C), with immunohistochemistry showing no evidence of significant staining loss (Figure 3D, 3E). The differential diagnosis included well-differentiated papillary mesothelioma, epithelioid peritoneal mesothelioma, and florid mesothelial hyperplasia, and a well-differentiated papillary mesothelioma was highly suspected. The management plan recommending debulking surgery followed by HIPEC was proposed by the multidiscipline tumor board. However, the patient declined the suggested treatment due to her wish to preserve fertility. Six months after the initial presentation, she returned to the clinic for embryo transfer surgery, aiming to address her fertility aspirations. During the preoperative evaluation, the incidental finding of ascites prompted a referral to Taipei Medical University Hospital for further assessment. A CT scan performed on July 8, 2020 revealed a newly-enlarged right inguinal lymph node measuring 1.8 cm, along with a persistent soft-tissue density in the adnexa and a stable peritoneal nodule, with no significant interval changes compared to the CT scan conducted on February 26, 2020.

Subsequent diagnostic laparoscopy included the excision of tumors from the small intestine and omentum, with the tumors measuring 1 cm and 2 cm, respectively. Notably, the tumor in the omentum exhibited invasion into the muscularis propria. Additionally, miliary tumors were observed on the right pelvic peritoneum, cul-de-sac, and diaphragm, accompanied by the presence of dark-brownish ascites. Histopathological examination of specimens (Figure 4) from the peritoneum, large intestine, and small intestine revealed proliferative mesothelial cells with a finely granular chromatin pattern. Invasion into the subserosa and muscularis propria of the large intestine and omentum was confirmed. Immunohistochemical staining was positive for calretinin and BAP1, consistent with a final diagnosis of low-grade epithelioid peritoneal mesothelioma, staged as pT3NxMx (IIIB).

ONCOLOGICAL COURSE AND TREATMENT:

Following the diagnostic procedure, the patient elected to undergo chemotherapy instead of debulking surgery. She subsequently received 5 cycles of adjuvant chemotherapy, consisting of carboplatin at 5 AUC and paclitaxel at a dose of 175 mg/m², administered every 3 weeks between August 2020 and November 2020. The chemotherapy regimen was generally well-tolerated, with the patient experiencing only minor adverse effects, notably alopecia. No significant adverse effects such as pancytopenia, nausea, or vomiting were reported during treatment.

However, a follow-up fluorodeoxyglucose-positron emission tomography (FDG-PET CT) scan performed on October 15, 2020 (Figure 5), during the chemotherapy course indicated disease progression. The scan revealed an increase in the size of the right inguinal lymph node, suggesting progression of the underlying pathology.

On November 5, 2020, the patient underwent a laparoscopic fertility-sparing surgery aimed at excising malignant tumors from the abdominal wall and omentum. This procedure included HIPEC and excision of the right inguinal tumor (Figure 6). During the operation, multiple miliary tumors, ranging from 0.1 to 1 cm in size, were identified and excised from the abdominal wall and peritoneum. The right inguinal lymph node was also excised, and HIPEC was performed with paclitaxel (175 mg/m2) for 90 minutes. Pathological analysis of the excised specimens confirmed the presence of epithelioid-type mesothelioma involving the right pelvic cavity and omentum (Figure 7).

After chemotherapy proved ineffective, the patient underwent surgery again, combined with HIPEC (hyperthermic intraperitoneal chemotherapy) to remove visible tumors. During shared decision-making regarding treatment options, the patient declined further chemotherapy (including pemetrexed) and opted for dual immunotherapy instead. She was started on immunotherapy, receiving 3 cycles of nivolumab (100 mg) and ipilimumab (50 mg) every 4 weeks from December 2020 to February 2021. Throughout the immunotherapy course, she tolerated the treatment well, without experiencing significant adverse effects such as nausea, vomiting, or fever. Additionally, her estrogen and follicle-stimulating hormone (FSH) levels remained within normal ranges, suggesting preserved ovarian function despite the aggressive treatment regimen. Subsequent follow-up imaging studies, including CT and MRI scans, demonstrated stable soft-tissue densities in the bilateral adnexa. Importantly, there were no signs of malignancy or metastasis in the lungs or brain, providing reassurance of disease stability.

IN VITRO FERTILIZATION AND OBSTETRIC COURSE:

With no evidence of disease recurrence or metastasis, the patient proceeded with IVF and embryo transfer. This intervention culminated in a successful pregnancy in May 2022. Comprehensive prenatal evaluations, conducted at local hospital, confirmed the absence of gestational diabetes mellitus, preeclampsia, or proteinuria. Additionally, high-resolution ultrasound examinations confirmed normal fetal anatomical development.

However, at 29 weeks of gestation, she had preterm premature rupture of membranes (PPROM). She was subsequently admitted to our hospital for tocolytic therapy, receiving ritodrine and nifedipine to inhibit uterine contractions. To prevent infection, antibiotics were administered alongside beta-methasone to accelerate fetal lung maturation and magnesium sulfate for neuroprotection. Despite 5 days of intensive tocolysis, the patient continued to experience frequent uterine contractions. Concurrently, the amniotic fluid index (AFI) decreased significantly from an initial measurement of 4.82 at admission to 0, accompanied by bloody vaginal discharge and uterine contraction. Given these developments, an emergency cesarean section was performed at a gestational age of 30 weeks 2 days on Dec. 12, 2022. She delivered a female infant who weighed 1378 g, with Apgar score 7/9 at 1 and 5 mins. The neonate was kept in the intensive care unit with oxygen therapy, which was withdrawn when the oxygen saturation level was greater than 90%. She continued to feed well and grow appropriately during her stay. No imaging studies were required and she was subsequently discharged.

Following the delivery, a secondary surgical exploration by gynecologic oncologists was conducted to evaluate any potential tumor progression or metastasis within the abdominal cavity. Intraoperatively, multiple tumor seedings were identified, ranging from 0.5 to 1.5 cm in size, distributed across the small intestine, mesentery, and peritoneum. These lesions were excised, along with residual tumors located on the rectum, peritoneal wall, and bladder base. Biopsies were obtained, and pathological examination confirmed the presence of epithelioid peritoneal mesothelioma. Postoperatively, the patient remained stable without any anticancer treatment and was discharged with a plan for outpatient follow-up. The most recent imaging studies, including CT and MRI scans, revealed a uterine myoma measuring 4.5 cm, with no further evidence of malignancy elsewhere. The treatment timeline is presented in Figure 8.

Discussion

CLINICAL PRESENTATION, DIAGNOSIS AND MANAGEMENT OF MALIGNANT PERITONEAL MESOTHELIOMA (MPM):

Malignant mesothelioma is a rare but highly aggressive neoplasm originating from the serosal membranes. Its prevalence varies by anatomical site, with the pleura being the most commonly affected, followed by the peritoneum, pericardium, and testis, in descending order of frequency [4,10]. In contrast to the male predominance observed in pleural mesothelioma, the prevalence of malignant peritoneal mesothelioma (MPM) in females ranges between 30% to 50% in the United States [11]. While MPM is often associated with industrial pollutants, particularly asbestos exposure, this association is less pronounced than in pleural mesothelioma [12–14]. This suggests that MPM can develop even in the absence of significant asbestos exposure, potentially due to germline BAP1 heterozygous mutations, which are hypothesized to increase susceptibility to low levels of asbestos exposure [15]. MPM is histologically classified into 3 subtypes: epithelioid, sarcomatous, and biphasic. Among these, the epithelioid subtype is the most prevalent and is associated with the most favorable prognosis [11,16]. MPM is classified into 2 grades: low-grade and high-grade [14].

However, the clinical presentation of MPM is often nonspecific, with symptoms such as abdominal distension, pain, early satiety, anorexia, nausea, and weight loss, which do not distinctly point to this malignancy [17]. As a result, MPM is frequently discovered incidentally during routine examinations or unrelated surgical procedures, leading to delayed diagnosis and, consequently, advanced disease with abdominal seeding in many patients [11,18].

When malignancy is suspected, initial imaging typically involves computed tomography (CT) or magnetic resonance imaging (MRI). While these modalities effectively identify areas of concern, they lack the specificity required to definitively diagnose the type of cancer [19].

Positron emission tomography (PET) scans are often employed for staging purposes but do not offer definitive identification of MPM. Given the low diagnostic specificity of imaging studies, the definitive diagnosis of MPM relies on tissue sampling via CT-guided core-needle biopsy or laparoscopic biopsy, followed by histopathological examination and immunohistochemical analysis [18].

Hematoxylin-eosin (H&E) staining provides initial identification of the MPM subtype but is insufficient for distinguishing MPM from other malignancies such as non-small cell lung carcinoma, renal cell carcinoma, and ovarian carcinoma [20]. Consequently, immunohistochemistry (IHC) is essential in differentiating mesothelioma from its malignant mimics and other mesothelial proliferations [14].

A comprehensive IHC panel, typically including at least 2 mesothelial markers and 2 carcinoma-related markers, is employed to confirm the diagnosis [14]. Commonly utilized mesothelial markers include calretinin, WT-1, podoplanin, BAP1, MTAP, and CDKN2A. These markers are crucial for confirming the mesothelial origin of the tumor. Additionally, carcinoma-related markers such as CEA, claudin-4, Ber-EP4, MOC-31, and TTF-1 are utilized to further refine the diagnosis, distinguishing MPM from other carcinomas [14,16]. This immunohistochemical approach not only aids in accurate diagnosis but also has prognostic implications, particularly in the context of determining the most appropriate therapeutic strategy.

In recent years, advances in molecular diagnostics have further enhanced our understanding of malignant peritoneal mesothelioma (MPM), providing deeper insights into its pathogenesis and potential therapeutic targets. Genetic alterations, particularly involving the BAP1 gene, have emerged as significant contributors to the development and progression of MPM. BAP1 (BRCA1-associated protein 1) is a tumor-suppressor gene that plays a crucial role in various cellular processes, including DNA repair, cell cycle regulation, and chromatin remodeling [21]. Loss-of-function mutations in BAP1 are found in many MPM cases, especially in those without a history of asbestos exposure, highlighting its role in the tumorigenesis of mesothelioma [22].

The identification of BAP1 mutations has not only provided insights into the molecular underpinnings of MPM but also opened avenues for personalized medicine. Patients with BAP1 mutations may benefit from targeted therapies aimed at exploiting specific vulnerabilities associated with this genetic alteration [23]. For instance, recent studies have explored the potential of PARP inhibitors, which target DNA repair pathways, in BAP1-mutated mesotheliomas [24]. These developments are a significant step forward in the treatment of MPM, which has historically been challenging due to the disease’s resistance to conventional chemotherapy and radiation therapy.

Another promising area of research in MPM management is the use of immunotherapy, particularly immune-checkpoint inhibitors. Immune-checkpoint blockade, which involves targeting inhibitory receptors such as PD-1, PD-L1, and CTLA-4 on T cells, has revolutionized the treatment of various solid tumors [25]. The potential synergy between immunotherapy and other modalities, such as cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC), is also under investigation, with the goal of improving patient outcomes and prolonging survival [26].

Additionally, comprehensive genomic profiling can identify actionable mutations and inform the selection of targeted therapies, moving towards a more personalized treatment approach. Despite these advancements, the management of MPM remains complex and multifaceted, requiring a multidisciplinary approach. Optimal patient care involves not only accurate diagnosis and staging but also consideration of various treatment modalities, including surgery, chemotherapy, radiation, and emerging therapies such as targeted agents and immunotherapy. The ongoing development of clinical trials and translational research is critical to further refining therapeutic strategies and improving the prognosis of patients with MPM.

CRS AND HIPEC IN TREATMENT OF MALIGNANT PERITONEAL MESOTHELIOMA:

Malignant peritoneal mesothelioma (MPM) remains a challenging and aggressive malignancy with limited treatment options. The current therapeutic strategies for MPM include surgical intervention and systemic therapies [27], with cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) emerging as the cornerstone of treatment in select patients. This approach is particularly recommended for individuals with medically operable, diffuse peritoneal mesothelioma and those demonstrating good performance status, following a comprehensive multidisciplinary evaluation [27–29].

CRS aims to surgically remove all visible tumor deposits within the peritoneal cavity, thereby reducing the tumor burden to the lowest possible level. This is followed by HIPEC, which involves the circulation of heated chemotherapeutic agents directly within the abdominal cavity to target residual microscopic disease. The rationale behind HIPEC lies in the enhanced penetration of chemotherapeutic agents at elevated temperatures, which may also potentiate their cytotoxic effects on cancer cells. This combined modality treatment has been shown to significantly improve survival outcomes in patients with MPM [28,29].

Several studies have demonstrated the efficacy of CRS and HIPEC, with median overall survival for patients undergoing these procedures ranging from 38.4 to 63.2 months [29–33]. The 3-year and 5-year survival rates reported in the literature vary between 42% and 60% and 42% and 50.2%, respectively. These findings underscore the potential of CRS and HIPEC not only to extend survival but also to offer durable control of disease in a subset of patients with MPM [30–33].

The decision to pursue CRS and HIPEC is based on multiple factors, including the depth of tumor invasion, histological subtype, patient age, and overall health status [29]. The success of this approach is highly dependent on the completeness of cytoreduction, with more extensive tumor debulking correlating with better outcomes. However, the procedure is not without risks, and patient selection remains critical to optimizing results. The potential benefits of this aggressive therapy must be weighed against the risks, particularly in patients with comorbidities or advanced age.

SYSTEMIC THERAPY IN THE MANAGEMENT OF MALIGNANT PERITONEAL MESOTHELIOMA:

For patients with malignant peritoneal mesothelioma (MPM) who are not candidates for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), systemic therapy remains the cornerstone of treatment. This group includes individuals who are deemed inoperable due to factors such as extensive disease involvement, including bicavitary dissemination, or those with histological subtypes associated with a poorer prognosis, such as sarcomatoid or biphasic histology [34–36].

Systemic therapy typically involves use of chemotherapeutic agents aimed at controlling tumor growth, alleviating symptoms, and prolonging survival. Pemetrexed, a multi-targeted antifolate, has emerged as a key agent in the systemic treatment of MPM, particularly when combined with platinum-based chemotherapy such as cisplatin [37]. This regimen is commonly employed as a first-line therapy, especially for patients who are not eligible for surgical intervention [38].

Several clinical trials have evaluated the efficacy of pemetrexed-based regimens in MPM, both as monotherapy and in combination with cisplatin. These studies have reported median overall survival ranging from approximately 13 to 16.6 months, demonstrating the potential of systemic therapy to offer meaningful clinical benefits in this challenging patient population [34,36,39–41]. Additionally, the 1-year survival rates for patients receiving these regimens have been reported to range between 41.5% and 51.4% [42]. These outcomes, while modest compared to those achieved with CRS and HIPEC, underscore the importance of systemic therapy in managing patients with advanced or inoperable MPM.

In recent years, ongoing research has sought to optimize systemic treatment strategies for MPM, including the exploration of novel combinations and the integration of emerging therapies such as immunotherapy. Immune-checkpoint inhibitors targeting PD-1, PD-L1, and CTLA-4 have shown promise in other mesothelioma subtypes and are now being investigated in the context of peritoneal mesothelioma [43,44].

Despite these advances, the management of MPM with systemic therapy remains complex, and response rates vary depending on factors such as tumor biology and patient performance status. Personalized approaches that incorporate molecular profiling and the identification of predictive biomarkers are increasingly recognized as essential in guiding treatment decisions and maximizing therapeutic efficacy.

THE ROLE OF IMMUNE-CHECKPOINT INHIBITORS IN TREATMENT OF PERITONEAL MESOTHELIOMA:

The exploration of ICIs in the treatment of peritoneal mesothelioma, although constrained by small sample sizes, has shown promising potential. Immune-checkpoint blockade, particularly targeting the PD-1/PD-L1 axis, has garnered significant attention due to its effectiveness in other malignancies, and recent studies have sought to extend these benefits to peritoneal mesothelioma. Atezolizumab, a PD-L1 inhibitor, has been evaluated in combination with bevacizumab, an anti-VEGF agent, as a second-line therapy for patients with peritoneal mesothelioma. In this setting, the combination therapy demonstrated a 1-year overall survival rate of 85% and a median response duration of 12.8 months [45]. This regimen appears particularly promising given the typically poor prognosis associated with peritoneal mesothelioma and the limited efficacy of existing therapies.

Avelumab, another PD-L1 inhibitor, has also shown potential as a second-line treatment. Notably, its efficacy appears to be enhanced in tumors that express PD-L1, with these patients exhibiting a higher response rate compared to those without PD-L1 expression [46]. This finding underscores the importance of biomarker-driven therapy in optimizing treatment outcomes for peritoneal mesothelioma.

In addition to PD-1/PD-L1 inhibitors, CTLA-4 inhibitors such as ipilimumab have been investigated for their therapeutic potential. Ipilimumab has been studied both as a monotherapy and in combination with other ICIs such as nivolumab. These combination regimens have shown significant clinical benefit, with median overall survival ranging from 10.2 to 19 months and a 1-year survival rate of 68% [47,48]. The combination of ipilimumab and nivolumab, in particular, is a synergistic approach that enhances the anti-tumor immune response, offering hope for improved outcomes in this challenging malignancy.

Despite these encouraging results, the limited data available on the use of ICIs in peritoneal mesothelioma preclude their widespread adoption as first-line therapies. Current evidence has not conclusively demonstrated that ICIs alone or in combination are superior to traditional chemotherapy in the initial treatment setting. However, the U.S. Food and Drug Administration (FDA) approved the combination of the PD-1 inhibitor nivolumab and the CTLA-4 inhibitor ipilimumab for unresectable pleural mesothelioma in 2020, suggesting a potential future role for similar strategies in peritoneal mesothelioma.

This approval for pleural mesothelioma may pave the way for broader applications in peritoneal mesothelioma, particularly as more data become available. Ongoing clinical trials and expanded studies are crucial to determining the optimal use of ICIs in this context and may eventually establish these therapies as a standard part of the treatment arsenal against peritoneal mesothelioma.

IMMUNE-RELATED ADVERSE EVENTS (IRAES) AND FERTILITY CONSIDERATIONS IN IMMUNOTHERAPY:

While ICIs have revolutionized the treatment landscape for various malignancies, the potential for irAEs remains a significant concern that must be carefully managed [49,50]. irAEs arise from the immune system’s hyperactivation, leading to off-target effects that can impact multiple organ systems. The incidence and severity of irAEs vary, with dermatologic toxicities such as pruritus and rash being among the most common manifestations [51].

Other common manifestations include lower digestive tract issues [52,53] (eg, diarrhea, colitis), hepatotoxicity [54] and endocrinopathies [55,56] (eg, hypophysitis, thyroid dysfunction). Despite the clinical effectiveness of treatment, irAEs cannot be ignored. The impact of irAEs is broad, affecting various organ systems through immunological enhancement and suppression. One of the most common irAEs is dermatologic toxicity, such as pruritus and rash [51].

The cardiovascular system can also be affected by irAEs, but these events are less common than dermatologic or gastrointestinal manifestations. Cardiotoxicity associated with ICIs may present as myocarditis, pericarditis, or even arrhythmias, and while rare, these conditions can be severe and potentially life-threatening. Cardiovascular irAEs require prompt recognition and management, often necessitating discontinuation of ICIs and initiation of immunosuppressive therapy [57,58].

Renal toxicity is another important irAE that clinicians must monitor for. Nephritis induced by ICIs can lead to acute kidney injury, which may necessitate cessation of therapy and the use of corticosteroids or other immunosuppressants to mitigate damage [59]. The renal system’s vulnerability to irAEs underscores the need for regular monitoring of renal function throughout the course of ICI therapy.

Pulmonary toxicity, including pneumonitis, is a well-documented irAE and can range from mild interstitial changes to severe, life-threatening inflammation requiring hospitalization. Patients presenting with respiratory symptoms such as cough, dyspnea, or chest pain during ICI therapy should be promptly evaluated for pneumonitis, with imaging studies and pulmonary function tests as necessary. The management of pneumonitis often involves corticosteroids and discontinuation of ICIs, with the decision to resume therapy carefully weighed against the risks of recurrence [60,61].

In the context of endocrinopathies, irAEs can lead to a wide spectrum of dysfunctions involving the pituitary, thyroid, adrenal glands, and pancreas. Hypophysitis, a common endocrine-related irAE, may present with symptoms of headache, fatigue, and visual disturbances and can result in secondary adrenal insufficiency [62]. Thyroid dysfunction, including hypothyroidism and hyperthyroidism, is frequently observed and may necessitate lifelong thyroid hormone replacement therapy [63]. Furthermore, adrenalitis can manifest as adrenal insufficiency, requiring prompt glucocorticoid replacement. The impact of these endocrine irAEs can be profound, affecting the patient’s quality of life and requiring ongoing management even after discontinuation of ICIs [64].

The reproductive system is not immune to the effects of irAEs. While data on the direct impact of ICIs on fertility are still emerging, there is growing concern about potential gonadal toxicity, particularly in women of childbearing age. Fertility preservation strategies, including sperm banking for men and oocyte or embryo cryopreservation for women, are recommended before initiating ICI therapy in patients with reproductive concerns. These proactive measures can help mitigate the potential long-term consequences of treatment on fertility [65].

For pregnant patients or those planning pregnancy, the use of ICIs poses unique challenges. Given the crucial role of the immune system in maintaining fetomaternal tolerance, the administration of ICIs during pregnancy raises concerns about the potential for immune-mediated pregnancy complications such as spontaneous abortion, preterm labor, or fetal growth restriction. Recently, human studies have shown that ICI use during pregnancy may be better tolerated than previously suspected [66].

In clinical practice, the decision to use ICIs in pregnant patients must be made on a case-by-case basis, with a thorough assessment of the risks and benefits. For women undergoing ICI therapy who are considering pregnancy, it is generally advised to delay conception until at least 6 months after the completion of treatment to allow for resolution of irAEs and stabilization of the immune system [67]. This precaution helps to minimize potential risks to both the mother and the fetus. Additionally, healthcare providers should engage in discussions with patients about fertility preservation options before starting ICI therapy, especially in younger patients who may wish to have children in the future.

Conclusions

This report presents the case of a 44-year-old nulliparous woman diagnosed with low-grade epithelioid MPM, discovered incidentally during a laparotomic myomectomy. Initial imaging and histopathological assessments confirmed the diagnosis, with immunohistochemistry revealing positivity for calretinin and BAP1. Despite the recommendation for debulking surgery and HIPEC, the patient opted for fertility preservation, influencing her treatment decisions. Following chemotherapy and immunotherapy, the patient delivered a premature female baby with healthy outcome. This review illustrates the delicate balance between managing a serious cancer diagnosis and preserving fertility. It highlights the importance of personalized treatment plans, especially when patients face challenging decisions that impact both their health and future family plans. The successful outcome in this case, with the patient delivering a healthy baby, underscores the potential for favorable results of immunotherapy even in complex situations.