Diagnosis by laparoscopy: a case report of peritoneal lymphomatosis secondary to Burkitt lymphoma in a patient with suspected ovarian cancer

Introduction

Peritoneal lymphomatosis is a rare extranodal presentation of high-grade lymphomas that invade the peritoneum. Only 1.75% of non-Hodkin’s lymphomas involve the peritoneum and omentum at initial presentation (1). Furthermore, peritoneal lymphomatosis most commonly occurs secondary to diffuse large B-cell lymphoma and more rarely due to Burkitt lymphoma. Burkitt lymphoma is a particularly aggressive cancer with a short doubling time of 25 hours, making it very responsive to chemotherapy (2). High-intensity short-duration chemotherapy cycles with appropriate prophylaxis and monitoring for tumor lysis syndrome are largely successful if initiated promptly, with remission rates ranging from 75–90% and overall survival rate is 50–70% in adults (2).

Peritoneal lymphomatosis is a challenging diagnosis because it closely mimics peritoneal carcinomatosis, which is more commonly seen in gastrointestinal and ovarian cancers. Clinically, both can present with constitutional symptoms, abdominal distension, and ascites. Additionally, both can present with omental nodularity, ascites, and lymphadenopathy on imaging. Histology remains the gold standard for differentiating peritoneal lymphomatosis and carcinomatosis. While peritoneal lymphomatosis is more rare than peritoneal carcinomatosis, it is important to include both on the differential because treatment and prognosis are vastly different. Here, we present a case, in accordance with the CARE reporting guidelines, of peritoneal lymphomatosis secondary to Burkitt lymphoma that was diagnosed on omental biopsies performed laparoscopically. We present this article in accordance with the CARE reporting checklist (available at https://aol.amegroups.com/article/view/10.21037/aol-25-14/rc).

Case presentation

The patient is a 45-year-old female with no significant past medical history who presented with chief complaint of worsening abdominal distention for one week. Her abdominal distension was associated with palpitations, shortness of breath, bloating, constipation, abdominal cramping, nausea, decreased exercise tolerance, and mild urinary retention. She endorsed a weight loss of 13 pounds over the prior 4 months, which she attributed to healthier eating. She admitted to early satiety. She denied hematemesis, hematuria, hemoptysis, fever, chills, or night sweats. She denied the usage of tobacco, recreational drugs, or excessive alcohol intake. She did not have health insurance at the time of admission, so she was enrolled in a financial assistance program with discounted healthcare services. She denied any family history of colorectal or ovarian cancer.

At presentation, she was afebrile, tachycardic at 125 beats/minute, and hypertensive to 162/91 mmHg. On physical exam, she had notable abdominal distension without tenderness, rebound, guarding, or appreciable masses/lymphadenopathy. Otherwise, her physical exam was benign. Initial complete blood count (CBC) and comprehensive metabolic panel (CMP) were within normal limits aside from a transaminitis with an alanine transaminase (ALT) of 83 U/L, an aspartate transaminase (AST) of 69 U/L, and a total bilirubin of 1.4 mg/dL. Prompt computed tomography (CT) imaging of the abdomen and pelvis showed diffuse peritoneal and greater omental thickening, nodularity, and small-moderate volume of complex ascites consistent with peritoneal carcinomatosis (Figure 1). Furthermore, the CT showed extensive pelvic fat stranding without evidence of a dominant mass and an enhancing nodule located just lateral to the greater curvature of the stomach that measured 1.4 cm in short axis. The patient was admitted to Internal Medicine for expedited workup of a presumed gastrointestinal or ovarian cancer given imaging concerning for peritoneal carcinomatosis. A transvaginal ultrasound was performed, which was limited due to the extensive peritoneal nodularity that could not be seen separate from the ovaries. A gastrointestinal workup of an esophagogastroduodenoscopy and colonoscopy was performed, and both were negative for intestinal metaplasia, dysplasia, and malignancy. The patient was transferred to the Gynecologic Oncology service for workup and treatment of presumed ovarian cancer (Figure 2).

Figure 1 CT abdomen and pelvis with IV contrast showing omental thickening, nodularity, and enhancement. CT, computed tomography; IV, intravenous.

Figure 2 Timeline of clinical presentation. C1D1, cycle 1, day 1; CSP, colonoscopy; CT, computed tomography; DA-EPOCH-R, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab; EGD, esophagogastroduodenoscopy; MR, magnetic resonance.

Initial tumor markers including elevated lactate dehydrogenase (LDH) and carbohydrate antigen 125 (CA-125) further supported a diagnosis of malignancy (Table 1). A paracentesis yielded 1,900 mL of slightly cloudy ascitic fluid with atypical lymphocytes and few unidentified atypical cells seen on microscopy. The serum-ascites albumin gradient (SAAG) was calculated to be 0.9, consistent with an exudative cause. LDH was markedly elevated at 515 U/L and glucose was low at 44 mg/dL. Immunohistochemical (IHC) stains were initiated on the ascitic fluid. Three days later, she underwent CT-guided core biopsy of an omental mass with Interventional Radiology. Initial results were limited, but without evidence of carcinoma. An additional therapeutic paracentesis was performed 5 days after the initial study, yielding 1,650 mL bloody fluid. Given her elevated CA-125, discrepancy between imaging and pathology, and clinical concern for ovarian cancer, Gynecologic Oncology proceeded with exam under anesthesia, diagnostic laparoscopy, and omental and peritoneal biopsies for definitive diagnosis.

The exam under anesthesia revealed normal external female genitalia, an approximately 8 cm fixed posterior pelvic mass separate from the rectum, fundus not easily palpable on exam, cervix deviated anteriorly and flush with vagina, and intrauterine device strings palpable in cervix. Upon laparoscopic entry into the abdomen, approximately 1,500 mL of diffusely bloody ascites was aspirated. Examination of the omentum showed significant smooth surfaced nodularity and cobble stoning, as seen in Figure 3. The omentum was friable, thick, and nodular. There were no adhesions to the bowel. The pelvis contained a large mass in the right adnexa that was friable and measured approximately 7 cm, as seen in Figure 4. Two omental biopsy samples and one peritoneal nodule biopsy were taken. An intraoperative frozen section biopsy revealed sheets of atypical small round blue cells concerning for lymphoma.

Figure 3 Intraoperative picture of diffuse omental nodularity and frank bloody ascites.

Figure 4 Intraoperative picture of uterus, peritoneal nodularity, and friable pelvic masses.

Cytology of the initial ascitic fluid sample resulted on post-op day 1, revealing atypical CD20⁺ lymphocytes suspicious for B-cell lymphoproliferative disorder. The laparoscopy-directed biopsy samples were sent for lymphoma workup. Histologic sections revealed fibroadipose soft tissue extensively involved by lymphoma. Flow cytometric analysis revealed a monoclonal CD10⁺ B-cell population. IHC stains of omental and peritoneal biopsies demonstrated a diffuse infiltrate of intermediate-sized B-cells that expressed CD10, CD20 and BCL6 but not BCL2, CD34, MUM1, and TdT. Ki-67 showed proliferation rate of >95%. Cytogenetic analysis was aborted due to lack of mitotic activity in the cultured sample. Fluorescence in situ hybridization (FISH) was positive for a MYC 5' deletion (Figure 5) and a t(8;14) IGH::MYC gene fusion (Figure 6) without evidence of rearrangement of BCL2 or BCL6 genes, consistent with Burkitt lymphoma. A bone marrow biopsy was not performed.

Figure 5 FISH depicting MYC 5' deletion in 58% of cells (c-MYC break-apart probe). Red: centromeric to c-MYC, 8q24. Green: telomeric to c-MYC, 8q24. Manual scoring method: 29/50 nuclei scored with demonstrated deletion, statistically significant cut-off of 11.6% (range: 5.8–18.2%). Magnification, 60×. FISH, fluorescence in situ hybridization.

Figure 6 FISH depicting MYC/IgH/CEN8 t(8;14) in 52% of cells. Red: MYC gene (8q24). Green: IGH gene (14q32). Aqua: CEN8 (Trisomy 8). Manual scoring method: 26/50 nuclei scored with demonstrated red-green fusion, statistically significant cut-off of 9.0% (range: 5.8–18.2%). Magnification, 60×. FISH, fluorescence in situ hybridization.

After the diagnosis of Burkitt lymphoma, the patient received one cycle of the chemotherapy regimen DA-EPOCH-R (rituximab, doxorubicin, etoposide, vincristine, cyclophosphamide, and prednisone). She was treated for tumor lysis syndrome, neutropenic typhlitis, and angioedema secondary to piperacillin-tazobactam/morphine. Her hospital course was otherwise complicated by a cranial nerve VI palsy and headache that prompted a CT head and magnetic resonance imaging (MRI) brain and orbits. Imaging subsequently revealed a mass in the right cavernous sinus measuring 1.6 cm × 1.2 cm × 1.2 cm, which was consistent with central nervous system (CNS) involvement by Burkitt lymphoma. Given her CNS involvement, she was diagnosed with stage IV Burkitt lymphoma. Patient received one intrathecal dose and one high dose of methotrexate for CNS involvement. She was transitioned to R-CODOX-M (rituximab, cyclophosphamide, vincristine, doxorubicin, and methotrexate)/R-IVAC (rituximab, ifosfamide, etoposide, and cytarabine) as the preferred regimen for patients with CNS involvement who are eligible for intensive chemotherapy. Following her first cycle of R-IVAC, she underwent positive emission tomography (PET) and MRI of the brain to assess for disease status, which revealed minimal residual mildly avid peritoneal nodularity and near resolution of the lesion involving her cavernous sinus. She subsequently received an additional cycle of R-IVAC and one cycle of R-CODOX-M. She had no evidence of disease on PET imaging 6 months after treatment completion with a Deauville score 1, as seen in Figure 7.

Figure 7 CT portion of PET/CT done 6 months post-treatment showing resolution of omental thickening, nodularity, and enhancement. CT, computed tomography; PET, positive emission tomography.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives after all possible attempts were made. The patient could not be reached by multiple methods of communication.

Discussion

Peritoneal lymphomatosis is a rare extranodal presentation of high-grade lymphomas that involve the peritoneum and closely mimic peritoneal carcinomatosis. In this case, initial CT findings were highly suggestive of peritoneal carcinomatosis and prompted an appropriate workup for malignancy of gastrointestinal or ovarian etiology. A subsequent diagnostic laparoscopy revealed the final diagnosis of Burkitt lymphoma. Initial lab work supported the diagnosis of a malignancy due to the exudative ascites on paracentesis and elevated CA-125. While CA-125 is sensitive for ovarian carcinoma, it is not specific, since CA-125 is a glycoprotein secreted by the normal epithelium that lines the peritoneum (3). Thus, the tumor marker CA-125 can be elevated in inflammatory processes and other malignancies such as peritoneal lymphomatosis (4).

Peritoneal lymphomatosis closely mimics peritoneal carcinomatosis, but there are certain radiological findings that support the diagnosis of peritoneal lymphomatosis compared to carcinomatosis. Diffuse lymphadenopathy, splenomegaly, and a large mesenteric mass are more suggestive of peritoneal lymphomatosis (5,6). Diffuse lymphadenopathy was not seen in this case as only one potential lymph node or peritoneal nodule of 1.4 cm was described, and it would not be classified as a large mesenteric mass or mass >2 cm (6). The large bulky homogeneous masses characteristic of peritoneal lymphomatosis could only be appreciated by diagnostic laparoscopy where they were not obscured by fat stranding, ascites, and peritoneal nodules. There was no evidence of splenomegaly on imaging in this case. As seen in this case, peritoneal lymphomatosis and carcinomatosis can both present with omental caking and large volume ascites (7). Due to the overlapping features on imaging, both peritoneal lymphomatosis and carcinomatosis should be included in the differential diagnosis. Other more rare diagnoses that can be considered are peritoneal sarcomatosis and tuberculosis peritonitis (8). It is critical to acquire a quality tissue biopsy that can differentiate these different pathologies and dictate appropriate management.

Tissue biopsy is the gold standard for the diagnosis of peritoneal lymphomatosis, and timely diagnosis can help expedite treatment. Because this patient had an isolated peritoneal nodule, a CT-guided biopsy was performed but the sample was not sufficient for the diagnosis of lymphoma. As seen in other case reports, biopsies from diagnostic and even exploratory laparotomies have helped expedite the final diagnosis and initiation of chemotherapy (4,8-11). Because lymphoma is curable by chemotherapy alone and prior cytoreductive surgeries have resulted in negative outcomes, it is important that laparoscopies are conducted for the purpose of biopsies and additional imaging (9). The omental and peritoneal biopsies obtained at the time of laparoscopy allowed for flow cytometry, IHC stains, and FISH studies to achieve the proper diagnosis of Burkitt lymphoma so that the first cycle of chemotherapy could be initiated during the patient’s hospitalization.

The importance of a timely diagnosis for peritoneal lymphomatosis is critical because high-grade non-Hodgkin’s lymphomas are aggressive and metastasize quickly. From case reports of peritoneal lymphomatosis, many patients have died from tumor progression, complications from tumor lysis syndrome, or sepsis secondary to immunodeficiency (4,10-16). Since lymphomas such as Burkitt lymphoma grow so rapidly, prompt treatment is critical to prevent metastases and increased tumor burden that carry a higher risk of complications. For instance, this case highlights the rapid progression of Burkitt lymphoma as evidenced by the development of a right cavernous sinus tumor during her initial hospitalization. Fortunately, the diagnosis of Burkitt lymphoma allowed for the patient to receive proper treatment for her cancer, tumor lysis syndrome, and subsequent opportunistic infections so that the patient could be without refractory disease currently.

Conclusions

In conclusion, this case report highlights the importance of including peritoneal lymphomatosis in a differential for imaging that shows omental caking, ascites, and peritoneal nodularity without evidence of another primary tumor. Furthermore, our case had overlapping features with peritoneal carcinomatosis on imaging, highlighting the importance of prompt tissue biopsy as the gold standard for peritoneal lymphomatosis diagnosis. If core needle biopsies are not sufficient for diagnosis, diagnostic laparoscopy remains a viable option that should be considered for timely diagnosis of peritoneal lymphomatosis. Peritoneal lymphomatosis can occur with aggressive lymphomas and can be treated with chemotherapy without the need for cytoreductive surgery to induce remission and better survival outcomes.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://aol.amegroups.com/article/view/10.21037/aol-25-14/rc

Peer Review File: Available at https://aol.amegroups.com/article/view/10.21037/aol-25-14/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://aol.amegroups.com/article/view/10.21037/aol-25-14/coif). C.M.S. received grants from the ASRM Diversity, Equity, and Inclusion Committee to advance Diversity, Equity, and Inclusion efforts within the society (payment was made to the institution); received support for attending meetings and/or travel from American College of Obstetrics and Gynecology (ACOG); and served as the Section V District XI Junior Fellow Vice Chair of ACOG. G.M. received grant from CPRIT Award RP260516, improving access to risk-reducing opportunistic salpingectomy in South Texas. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent for publication of this case report and accompanying images was not obtained from the patient or the relatives after all possible attempts were made. Patient could not be reached by multiple methods of communication.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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