Non-Hodgkin Lymphoma Presenting as Peritoneal Lymphomatosis: A Case Report

Discussion

Extensive infiltration of the peritoneum by lymphomas is rare, more commonly seen in high-grade NHL, with only a few cases documented in the literature. The earliest report dates back to 1986, describing a necropsy study of three such patients.⁸ In an analysis of 101 cases of malignant ascites confirmed cytologically, only eight involved NHL (8%).⁸ Similarly, in a series of 100 patients with ascites, lymphoma was the cause in just 2%.⁹ A study of 400 patients with newly diagnosed or recurrent NHL found peritoneal and omental involvement in seven patients (1.75%), with four patients (1%) presenting with ascites.⁶ An autopsy series of 322 disseminated lymphoma cases revealed peritoneal and omental disease in 64 cases (20%).¹⁰ The rarity of peritoneal involvement by lymphoma is because this tissue lacks lymphoid elements. Recognizing this uncommon manifestation is crucial for accurate diagnosis and optimal treatment.

Fujimi et al.¹¹ reported 46 cases of PL documented since 2001. The median age at onset was 55, with 76% being male. The most common histopathological type was DLBCL, observed in 20 cases, with 83% showing an aggressive phenotype. Lymphadenopathy was present in 16 cases, mostly localized to the abdomen (14 cases). Digestive tract infiltration was identified in 12 cases.¹¹ Similarly, our case also highlights the predominance of the DLBCL subtype of NHL, affecting abdominal lymph nodes and potentially infiltrating the digestive tract. Although upper endoscopy with biopsy excluded primary lymphoma of the proximal gastrointestinal tract, CT showed bowel thickening. Without a biopsy report, we cannot conclusively exclude the possibility of primary intestinal lymphoma infiltrating the peritoneum. On the other hand, although a colonoscopy was considered during the diagnostic process, considering the melena and the lack of findings on upper digestive endoscopy to explain this symptom, it was not performed. Priority was given to laparoscopic peritoneal biopsy, as it was believed this procedure might yield a definitive diagnosis.

Several imaging modalities play a role in the evaluation of patients with suspected or proven peritoneal disease. In general, CT is the first-line imaging modality in peritoneal disease due to its high availability, cost-effectiveness, and spatial resolution. However, CT has limited performance in evaluating small peritoneal implants (<1 cm).¹² On the other hand, the role of ultrasound is limited to confirming the presence of ascites, assessing for superficial peritoneal tumor deposits, and assisting with procedures such as percutaneous tissue or fluid sampling and drainage catheter placement.¹³ Magnetic resonance imaging (MRI) is the imaging modality of choice to explore anatomically difficult sites (e.g., subphrenic, mesenteric, and bowel serosa) and for detecting micronodular (<5 mm) and laminar patterns of peritoneal disease.¹⁴ PET/CT is a highly accurate method for detecting peritoneal disease, enabling visualization of tissues with radiotracer uptake, most commonly 18 F-2-deoxy-2-fluro-D-glucose (18F-FDG PET/CT).¹² In peritoneal lymphomatosis, 18F-FDG PET/CT has a higher sensitivity for detecting peritoneal involvement in subtle cases and greater accuracy in identifying extranodal sites other than the peritoneum, even in the absence of CT findings.¹⁵ New imaging methods to explore peritoneal disease include dual-energy CT (DECT), which can improve contrast resolution, and spectral photon-counting CT (SPCCT), which can achieve a spatial resolution of 250 μm.^12,13

The diagnosis of PL via CT is difficult, because its patterns often mimic those of other peritoneal conditions. PL typically shows diffuse smooth thickening of the peritoneum and mesenteric masses, which may or may not be accompanied by ascites.¹⁶ These features resemble peritoneal carcinomatosis, usually caused by the spread of primary tumors from the digestive or gynecologic organs, such as ovarian cancer, or from mucinous tumors like pseudomyxoma peritonei. Similar imaging characteristics are also seen in malignant primary peritoneal mesotheliomas, tuberculous peritonitis, sarcomatosis, diffuse peritoneal leiomyomatosis, and benign splenosis.⁷ Distinguishing features of PL, rather than peritoneal carcinomatosis, include lymphadenopathy, large mesenteric masses, ascites that is non-loculated and non-septated, as well as splenic or hepatic involvement and pleural effusion.^15,17

It is well known that serum LDH levels are elevated in many lymphoma types; and in primary gastrointestinal lymphoma, the LDH level at diagnosis serves as an independent prognostic biomarker.^3,18 However, no clinical studies currently define the relationship between PL and elevated ascitic LDH levels. Kim et al.¹⁹ reported that ascitic LDH levels can be elevated in some PL patients, supporting the idea that ascitic LDH might be a useful diagnostic clue. In our case, the presence of elevated LDH, protein in the ascitic fluid, low glucose levels, and sterile ascites corresponds with the clinical features observed in PL.

Serum CA-125 is a mucin-like glycoprotein antigen expressed in normal tissues originating from coelomic (such as pleura, pericardium, and peritoneum) and Müllerian (including fallopian tubes, endometrium, and endocervix) epithelium.²⁰ Elevated serum CA-125 levels can also occur in patients with pleural effusion or ascites regardless of the underlying cause, likely due to shear forces acting on mesothelial cells.¹⁸ Some case reports have also shown raised CA-125 levels in patients with PL.^{3,11,18,21–23} Our patient exhibited increased CA-125, yet no gynecological lesions were found during physical examination or CT scan, suggesting that the elevated serum CA-125 was probably related to this context PL.

Ascites cytology is a useful method for diagnosing malignant ascites, with a sensitivity of about 60% and a specificity of 100%.²⁴ Various reports have shown cytology can detect lymphoid cells and confirm PL diagnosis.^3,18,25–27 However, the overall sensitivity of cytology depends on the quality of the specimens examined. In a study involving eight patients with DLBCL and PL, cytology confirmed the diagnosis in only two cases.²⁸ Lynch et al.¹⁰ observed that cytology yielded a diagnosis in just one out of seven patients with NHL and PL. A review by Zhu et al.²¹ of 12 cases reported a single instance of PL diagnosis through ascites cytology. Additionally, lymphoma can cause significant mesothelial hyperplasia, which may complicate cytology interpretation and delay diagnosis.¹⁸ Thus, laparoscopic or image-guided needle biopsy remains the gold standard for definitive diagnosis.

Peritoneal lymphomatosis is aggressive. The disease remission rate is reported to range from 38% to 46%^11,21,29 The cause of death is either disease progression or tumor lysis syndrome.¹¹ The poor prognosis of primary PL may be due to its aggressive clinical course and the difficulty in diagnosis because of its similarity with other peritoneal diseases.¹¹ However, despite the high mortality rates, prompt and appropriate therapy can lead to long-term progression-free survival in some cases.²⁸ In this regard, our patient was treated with the R-CNOP regimen, which resulted in disease-free remission.

In summary, PL usually presents as aggressive histological subtypes of high-grade NHL, which can lead to rapid progression and worsening condition. Thus, early identification of this entity is crucial for prompt diagnosis and effective treatment that could improve survival. Careful evaluation of the clinical, analytical, and radiological features helps differentiate it from other conditions; however, a biopsy remains necessary for a definitive diagnosis.