Diagnostic and therapeutic challenges of Krukenberg tumors: Case report of an atypical presentation with obstructive renal failure

Abstract

Krukenberg tumors are rare metastatic ovarian neoplasms, most commonly originating from gastrointestinal adenocarcinomas, and are histologically characterized by mucin-producing signet-ring cells. Their clinical and radiological presentation is often nonspecific, which may delay diagnosis and complicate differentiation from primary ovarian malignancies. Imaging plays a crucial role in the initial assessment, with ultrasonography typically revealing bilateral or unilateral adnexal masses that are heterogeneous, predominantly solid, and associated with irregular margins and internal necrotic areas. Transvaginal ultrasound further refines lesion characterization by demonstrating a disorganized architecture with mixed solid and cystic components, highly suggestive of malignancy. Definitive diagnosis relies on histopathological examination supported by immunohistochemical profiling to identify the primary origin. Early recognition is essential given the poor prognosis and the need for multidisciplinary management. In this context, we report a case of a metastatic ovarian tumor consistent with a Krukenberg-type lesion.

Introduction

Krukenberg tumors are rare metastatic ovarian neoplasms, accounting for 1%-2% of all ovarian malignancies [1]. They most commonly arise from gastrointestinal adenocarcinomas, particularly gastric carcinoma, and are histologically characterized by mucin-producing signet-ring cells. These tumors often present with nonspecific symptoms such as pelvic pain, abdominal distension, or ascites, which can mimic primary ovarian malignancies, making early diagnosis challenging [1].

Imaging typically reveals large, often bilateral, solid-cystic ovarian masses, but radiology alone cannot reliably differentiate metastatic from primary tumors. Histopathological and immunohistochemical analyses, including CK7, CK20, CDX2, and SATB2, are essential to confirm the diagnosis and identify the primary site [1]. We report a case of a 58-year-old woman with bilateral large ovarian masses causing ureterohydronephrosis, highlighting the importance of early recognition and multidisciplinary evaluation for optimal management and prognostic assessment (Fig. 1, Fig. 2, Fig. 3).

Fig. 1.

Pelvic ultrasonography showing 2 large adnexal masses measuring 20 × 14 cm, and 10 × 7 cm. (A–D) Transabdominal (suprapubic) views demonstrate a voluminous, heterogeneous, and poorly defined lesion with irregular margins, predominantly solid components, and internal hypoechoic areas suggestive of necrosis, supporting a malignant process. (E and F) Transvaginal images provide higher-resolution characterization, revealing a disorganized, mixed solid–cystic, and infiltrative mass, highly suggestive of a secondary ovarian tumor consistent with metastatic ovarian involvement suggestive of a Krukenberg tumor.

Fig. 2.

Axial pelvic CT scan demonstrating (A, large white arrow) a large left abdominopelvic mass located superior and lateral to the uterus, suggestive of a left ovarian origin. The lesion showed a mixed solid–cystic pattern, measured approximately 17 cm in maximal diameter, and contained calcifications (B, small white arrow).

Fig. 3.

Pelvic magnetic resonance imaging demonstrating bilateral ovarian masses highly suspicious for metastatic ovarian involvement consistent with Krukenberg tumors. (A) Axial T2-weighted image reveals a large left adnexal mass (small arrow) measuring approximately 20 × 14 cm, a significant mass effect on the pelvic ureters (large white arrow) characterized by a predominantly solid architecture with heterogeneous signal intensity, irregular thickened septations, central cystic-necrotic degeneration, and diffusion restriction within the solid components. (B) Coronal section demonstrates a smaller right ovarian mass with predominantly solid tissue components, heterogeneous postcontrast enhancement, focal cystic changes, and restricted diffusion, associated with irregular margins and infiltration of the adjacent pelvic structures. (C) Sagittal image illustrates the marked locoregional mass effect on adjacent pelvic organs, associated moderate abdominopelvic ascites (red arrow), and nodular peritoneal thickening (small white arrow) suggestive of peritoneal carcinomatosis. Both ovarian lesions exhibited heterogeneous avid enhancement with a type III dynamic contrast-enhancement curve and were classified as O-RADS MRI 5, strongly supporting the diagnosis of malignant secondary ovarian involvement.

Case presentation

A 58-year-old married woman, gravida 3 para 3 (3 living children delivered vaginally), with a history of a triple-scarred uterus, presented with progressively worsening pelvic pain evolving over the previous 2 months. On admission, the patient was conscious and hemodynamically stable, with severe obesity (body mass index of 39 kg/m²). Gynecological examination revealed a large pelvic mass occupying the hypogastric region and extending up to the umbilicus. Speculum examination and vaginal digital examination were unremarkable.

Transvaginal ultrasonography demonstrated 2 large bilateral adnexal masses. The right ovarian mass measured approximately 10 × 7 cm and appeared predominantly solid with heterogeneous echogenicity and multiple internal cystic areas. The left ovarian mass measured approximately 20 × 14 cm and exhibited mixed solid-cystic components with irregular margins and central necrotic areas.

Contrast-enhanced abdominopelvic CT confirmed the presence of bilateral complex ovarian masses with heterogeneous enhancement. The left-sided lesion exerted a significant mass effect on the pelvic ureters, resulting in bilateral ureterohydronephrosis, more pronounced on the right side. Moderate ascites and diffuse peritoneal thickening suggestive of peritoneal carcinomatosis were also identified. In addition, regular circumferential thickening of the sigmoid colon wall measuring approximately 7 mm was observed.

Pelvic MRI provided further lesion characterization, demonstrating bilateral ovarian masses with predominant solid components, irregular thickened septations, heterogeneous postcontrast enhancement, diffusion restriction on DWI sequences, and central cystic-necrotic areas. The lesions exhibited a type III enhancement curve and were classified as O-RADS 5, highly suggestive of malignant ovarian involvement.

Laboratory investigations showed anemia with hemoglobin at 8.7 g/dL and a platelet count of 406,000/mm³. Renal function tests showed urea levels of 0.78-1.12 g/L and creatinine levels of 59.47 µmol/L at admission, with subsequent progressive elevation reaching 486 µmol/L during hospitalization, consistent with severe obstructive renal failure. Liver enzymes were within normal limits (AST 34 U/L, ALT 19 U/L), while inflammatory markers were elevated (CRP 78 mg/L). Blood group was A positive and irregular agglutinins were negative. Tumor marker analysis revealed a mildly elevated CA-125 level (36.8 U/mL), while CA19-9 was within normal limits (10 U/mL). The isolated elevation of AFP was considered nonspecific and may reflect tumor dedifferentiation or extensive tumor burden. Additional tumor markers including CEA, CA72-4, HE4, LDH, and β-hCG were unavailable.

In the context of progressive renal function impairment secondary to bilateral ureteral obstruction, the initial management consisted of the placement of bilateral double-J ureteral stents to restore urinary flow and bypass the extrinsic compression exerted by the large pelvic masses. Following placement of bilateral double-J ureteral stents, partial improvement in renal function and urinary drainage was observed. Given the suspicion of metastatic ovarian disease, particularly a Krukenberg tumor, a gastroenterology consultation was requested to investigate a potential primary gastrointestinal malignancy. Because colonoscopy was not technically available during the initial hospitalization, neither endoscopic biopsy nor CT colonography could be performed. Upper gastrointestinal endoscopy was not completed before the patient’s clinical deterioration. Consequently, the exact primary digestive site could not be formally identified.

Considering the high likelihood of malignancy and the inconclusive nature of noninvasive investigations, the patient subsequently underwent an exploratory laparoscopy with multiple peritoneal and tumor biopsies. Intraoperatively, the exploration revealed a large mass, preventing visualization of the uterus and adnexa, and was found to be adherent to the intestinal loops and the omentum. Multiple biopsies were obtained from the ovarian masses, peritoneal implants, and omentum for histopathological examination.

Histopathological examination revealed a malignant epithelial proliferation infiltrating the ovarian stroma and composed of mucin-producing signet-ring cells, consistent with metastatic adenocarcinoma of gastrointestinal origin. Immunohistochemical analysis demonstrated positive staining for CDX2 and CK7. Although this immunophenotype strongly supported a gastrointestinal primary tumor, particularly of gastric or pancreatobiliary origin, the exact primary site could not be definitively identified because additional immunohistochemical markers such as CK20, SATB2, PAX8, WT1, ER, and PR were not available, representing a limitation of the present case.

The postoperative course was initially uneventful. The patient was thereafter referred to the oncology department for further management, including histological characterization and therapeutic planning. However, the clinical evolution was marked by progressive deterioration of her general condition.

The patient ultimately died 1 month after her hospitalization due to cardiorespiratory arrest.

Discussion

Krukenberg tumors represent an uncommon subtype of ovarian malignancies, accounting for approximately 1%-2% of all ovarian tumors [2]. They correspond to metastatic ovarian deposits arising from mucin-producing adenocarcinomas, histologically characterized by the presence of mucin-filled signet-ring cells within a cellular ovarian stroma. Since the original description by Friedrich Krukenberg in 1896, these tumors have remained a diagnostic and therapeutic challenge because of their rarity, aggressive biological behavior, and frequent association with advanced metastatic disease [1].

The mechanisms underlying ovarian metastasis are not completely understood. Several hypotheses have been proposed, including lymphatic dissemination, hematogenous spread, and transcoelomic peritoneal seeding. Among these mechanisms, retrograde lymphatic spread from gastrointestinal malignancies has been considered one of the most plausible pathways explaining the high incidence of ovarian involvement in gastric carcinoma. Interestingly, in many cases the ovarian metastases are considerably larger than the primary tumor, suggesting that metastatic dissemination may occur at an early stage of the disease [1].

Krukenberg tumors predominantly affect women of reproductive age, with a mean age ranging between 40 and 45 years in most reported series [1,3]. Nevertheless, cases occurring in postmenopausal women have also been described, indicating that age alone should not exclude the diagnosis. Clinical manifestations are often nonspecific and may include pelvic pain, abdominal distension, menstrual irregularities, or symptoms related to ascites. Because these symptoms overlap with those of primary ovarian tumors, the diagnosis is frequently delayed. In a significant proportion of patients, ovarian metastases are detected before identification of the primary tumor, which contributes to the generally poor prognosis associated with this disease [1,4,5].

Radiological imaging plays an important role in the initial evaluation. Ultrasonography, computed tomography, and magnetic resonance imaging typically reveal large ovarian masses that are frequently bilateral and exhibit mixed solid and cystic components. Additional findings such as ascites, peritoneal implants, or lymphadenopathy may also be present. However, despite these suggestive features, imaging modalities alone cannot reliably distinguish primary ovarian tumors from metastatic lesions. Therefore, imaging findings must be interpreted in conjunction with clinical, biological, and histopathological data [6].

Histopathological examination remains the gold standard for establishing the diagnosis. The characteristic microscopic appearance includes mucin-containing signet-ring cells embedded within a hypercellular stromal background. Immunohistochemical studies are particularly useful in identifying the primary origin of the tumor when it is not clinically evident. Markers such as CK7, CK20, CDX2, and SATB2 are frequently used to differentiate gastrointestinal primaries from primary ovarian neoplasms, A CK7-positive/CK20-negative expression pattern is frequently associated with gastric or pancreatobiliary primaries, whereas a CK7-negative/CK20-positive profile combined with CDX2 positivity is more suggestive of a colorectal origin. Additionally, SATB2 has been reported as a highly specific marker for confirming colorectal differentiation [1].

Serum tumor markers may provide additional diagnostic information. CA-125 is the most commonly elevated marker in patients with Krukenberg tumors, although it lacks specificity. Elevated CA-125 levels have been correlated with tumor burden and disease progression in several studies, and some authors have suggested a potential prognostic value [2]. Nevertheless, tumor markers alone are insufficient for establishing the diagnosis.

In approximately 90% of cases, the primary tumor originates from the gastrointestinal tract. Gastric carcinoma represents the most frequent source, accounting for nearly 70% of cases, followed by colorectal cancers (10%-15%), pancreaticobiliary tumors, and appendiceal neoplasms [1,7]. Less commonly, primary tumors may arise from the breast, gallbladder, or urinary tract [8]. Consequently, when bilateral ovarian masses suspicious for metastases are identified, systematic investigation of the gastrointestinal tract, including upper and lower endoscopy is strongly recommended [1].

The optimal management of Krukenberg tumors remains controversial due to the absence of standardized treatment guidelines. Surgical treatment is generally considered the cornerstone of management when feasible and typically includes cytoreductive surgery with bilateral oophorectomy, hysterectomy, and omentectomy. Several studies have suggested that optimal cytoreduction may improve survival outcomes in selected patients, particularly when the metastatic disease is limited [1,9]. Systemic chemotherapy tailored to the primary tumor type is frequently administered as part of multimodal therapy. In contrast, radiotherapy has shown limited benefit in this clinical context [7].

Despite advances in oncologic therapies, the overall prognosis of Krukenberg tumors remains poor. Median survival reported in the literature generally ranges between 12- and 18-months following diagnosis. Prognosis is influenced by several factors, including the primary tumor origin, the presence of peritoneal carcinomatosis, ascites, and the feasibility of complete cytoreductive surgery [1,10].

Given the aggressive nature of this disease, early detection remains crucial. Some authors have emphasized the importance of systematic gynecological evaluation in women diagnosed with gastrointestinal malignancies, as well as careful intraoperative assessment of the ovaries during abdominal surgery for digestive cancers [11]. Conversely, the presence of bilateral ovarian masses associated with ascites should prompt thorough investigation for a possible gastrointestinal primary tumor [1]. Although prophylactic bilateral oophorectomy during surgery for gastrointestinal cancers has been proposed by certain authors, this approach remains controversial and requires further evidence before being routinely recommended [12].

Overall, Krukenberg tumors continue to represent a significant diagnostic and therapeutic challenge due to their rarity and aggressive clinical course. Reporting additional cases contributes to improving knowledge of their clinical presentation, facilitating earlier diagnosis, and optimizing management strategies.

Conclusion

Krukenberg tumors are rare metastatic ovarian tumors most frequently originating from gastrointestinal malignancies, particularly gastric carcinoma. Their clinical presentation is often nonspecific, and diagnosis is frequently delayed due to the difficulty in distinguishing them from primary ovarian tumors based solely on imaging findings. Histopathological and immunohistochemical analyses remain essential for confirming the diagnosis and identifying the primary tumor. Given their aggressive nature and poor prognosis, early recognition and a multidisciplinary management approach are crucial to optimize patient outcomes. Continued reporting of clinical cases and further research are necessary to improve understanding and therapeutic strategies for this uncommon but highly aggressive disease.

Learning points

• •Krukenberg tumors may present with atypical manifestations such as obstructive renal failure secondary to bilateral ureteral compression.
• •Bilateral ovarian masses associated with ascites and peritoneal disease should prompt investigation for a gastrointestinal primary tumor.
• •Imaging findings alone are insufficient to distinguish primary ovarian malignancies from metastatic ovarian disease.
• •Histopathology and immunohistochemistry remain essential for diagnosis and characterization of the primary origin.

Patient consent

The patient gave her informed and written consent for this case report to be published.