The difficult diagnosis of a patient presenting with a Krukenberg tumor and Lynch syndrome: a case report

A 35-year-old French Caucasian female patient presented to the general emergency department of our center with abdominal pain, bowel obstruction, and an altered general condition. Her medical history included a cholecystectomy and bipolar disorder, for which she was being treated with Xanax and Clozapine, and was followed in a day psychiatric hospital. Familial history revealed LS in her mother and maternal uncle, but the patient had never been screened for this owing to her poorly controlled bipolar disorder. Given the clinical presentation of intestinal obstruction and an inflammatory syndrome on her blood test, a contrast-enhanced abdominopelvic computed tomography (CT) scan was performed. The imaging revealed peritonitis with multiple peritoneal collections leading to segmental small bowel obstruction, raising suspicion primarily of peritoneal carcinomatosis or a chronic infectious process such as tuberculosis or actinomycosis (Fig.  1 ). The emergency physician initially consulted a gastrointestinal surgeon who, after reviewing the imaging, suggested a possible gynecological origin. Fig. 1 Contrast-enhanced abdominopelvic computed tomography scan showing two tissue-like masses (*) with peripheral enhancement Contrast-enhanced abdominopelvic computed tomography scan showing two tissue-like masses (*) with peripheral enhancement Subsequently, the patient was referred to the gynecological emergency department, where a transvaginal pelvic ultrasound (Fig.  2 ) revealed two abnormally enlarged ovaries (65 × 46 mm and 44 × 26 mm, respectively), raising the differential diagnosis of ovarian endometriomas. The patient was admitted to the gynecology department for further evaluation. Fig. 2 Endovaginal ultrasound showing the two masses (*) seen on the scanner Endovaginal ultrasound showing the two masses (*) seen on the scanner Owing to the possibility of a chronic infectious etiology, empirical broad-spectrum antibiotic therapy was initiated. A pelvic magnetic resonance imaging (MRI) scan (Fig.  3 ), performed on the seventh day of hospitalization owing to the lack of clinical improvement with antibiotics, revealed a tubo-ovarian abscess associated with a tumoral process in both ovaries. In addition, the patient’s Risk of Ovarian Malignancy Algorithm (ROMA) score was slightly elevated at 11.9% (N- ⩽ −11.4%), with an elevated CA-125 of 108 U/mL (N- < 35 U/mL) but a normal HE4 level of 59 pmol/L (N- < 92 pmol/L). Fig. 3 T2-weighted magnetic resonance imaging sagittal view showing the two ovarian masses. Two ovarian masses with a tissue-like appearance, measuring 39 × 45 mm on the left ( A ) and 68 × 56 mm on the right ( B ) T2-weighted magnetic resonance imaging sagittal view showing the two ovarian masses. Two ovarian masses with a tissue-like appearance, measuring 39 × 45 mm on the left ( A ) and 68 × 56 mm on the right ( B ) An exploratory laparoscopy was performed 2 weeks after the patient’s admission to obtain bacteriological and histopathological samples (Fig.  4 ). The surgery revealed extensive adhesions, two ovarian masses with a solid appearance, and peritoneal nodules suggestive of peritoneal carcinomatosis. No abnormalities were identified on the gastrointestinal tract. Histopathological examination of the peritoneal and ovarian biopsies (both right and left) revealed infiltration by a poorly differentiated adenocarcinoma, with an immunohistochemical profile suggestive of a colorectal origin (Fig.  5 a), along with a loss of MSH2 expression indicative of microsatellite instability (Fig.  5 b). The diagnosis of LS was confirmed through molecular genetic testing. Fig. 4 View of the exploratory laparoscopy. The two ovarian masses (*) on the right and left sides are visible ( a ). Residual omental-parietal adhesions are seen following adhesiolysis, which allowed access to the pelvic cavity ( b ) Fig. 5 a Peritoneal biopsy. Immunohistochemistry was positive for SATB2, suggesting a lower digestive origin. b Immunohistochemistry revealing a loss of MSH2 expression compared with normal mucosa View of the exploratory laparoscopy. The two ovarian masses (*) on the right and left sides are visible ( a ). Residual omental-parietal adhesions are seen following adhesiolysis, which allowed access to the pelvic cavity ( b ) a Peritoneal biopsy. Immunohistochemistry was positive for SATB2, suggesting a lower digestive origin. b Immunohistochemistry revealing a loss of MSH2 expression compared with normal mucosa To identify the primary tumor site, the diagnostic workup was extended with a positron emission tomography-computed tomography (PET-CT) scan and gastrointestinal endoscopies. The PET-CT scan revealed hypermetabolic and heterogeneous infiltration of the greater omentum with intergastro-splenic, peridigestive, and pelvic extension, as well as multifocal lateral aortic lymph node involvement. Esophagogastroduodenoscopy (EGD) did not identify any lesions. During colonoscopy, four colonic lesions and one rectal lesion were identified and biopsied. Histopathological analysis of these samples was consistent with the initial biopsies, confirming the primary tumor as a colorectal adenocarcinoma with ovarian metastases, namely a Krukenberg tumor. The patient was started on pembrolizumab, an anti-programmed cell death protein (PD)-1 monoclonal antibody, on the basis of the multidisciplinary consultation meeting’s recommendation. Subsequent reassessment with PET-CT showed a partial metabolic response to the therapy.

The medical team encountered several challenges in reaching the final diagnosis: the atypical clinical presentation and imaging initially suggested an infectious or tumoral etiology. The gynecological ultrasound raised the possibility of endometriosis. The patient’s complex psychiatric history, due to her bipolar disorder, delayed the discovery of her family history of Lynch syndrome. The surgical complexity further delayed the diagnosis, as multiple surgeons deemed the risk–benefit ratio unfavorable, given the high risk of intraoperative complications, particularly injury to adjacent organs. Indeed, the surgery was complicated by a bladder injury during the insertion of the suprapubic trocar. Lastly, the undocumented association between these two syndromes presented an additional diagnostic challenge. This case could allow us to rediscuss the potential overlap between Lynch syndrome and Krukenberg tumors. Finally this case show the possible coexistence of the two pathologies and must encourage diagnostic certainty using dedicated explorations such as molecular biology.

Krukenberg tumors (KT), defined as ovarian metastases typically originating from a primary gastrointestinal malignancy, represent only 1% of all ovarian tumors [ 1 ], but they complicate 4.6% of colorectal cancers in premenopausal women [ 2 ]. In addition, Lynch syndrome (LS) is associated with only 1% of ovarian tumors [ 3 ]. LS-related cancers predominantly involve the gastrointestinal tract (colorectal and small bowel), gynecological organs (endometrial and ovarian), urinary tract, and biliary-pancreatic pathways. The spectrum of Krukenberg tumors has expanded to include adenocarcinomas of the entire gastrointestinal tract. However, tumors considered to belong to Lynch’s syndrome remain excluded. A thorough literature review on PubMed did not reveal any similar cases of a patient with primary synchronous KT and LS.