Clinical Outcomes in Patients With Krukenberg Tumors From Colorectal Cancer.

INTRODUCTION: Ovarian metastases from gastrointestinal cancers such as colorectal cancer, also known as Krukenberg tumors (KTs), present unique challenges in management due to diagnostic uncertainty, decreased responsiveness to systemic therapies compared to other sites of metastasis, and associated debilitating symptomatology. Thus, we sought to characterize our institutional outcomes in metastatic colorectal cancer (mCRC) patients with KTs. METHODS: A retrospective single-institution study was performed identifying adult, female patients from 2012 to 2021 with a diagnosis of mCRC. Patient demographics and clinicopathologic characteristics were collected and analyzed. Descriptive statistics, univariate and multivariable analyses, and Kaplan-Meier survival analyses were performed. RESULTS: Of 235 mCRC patients, 45 (19.1%) had KTs, 41 (91.1%) of whom had KTs in conjunction with other metastatic sites. Other initial sites of metastasis included the liver (n = 93, 39.6%), lung (n = 28, 11.9%), and peritoneum (n = 18, 7.7%). In the KT cohort, the median age was 48 y, 53.3% were non-Hispanic White, 100% had microsatellite stable tumors, 33.3% had Kristen Rat Sarcoma Virus (KRAS) mutations, and 6.7% had V-raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) mutations. Fifty five point six percent of KT patients underwent cytoreductive surgery (CRS), 24.4% underwent palliative debulking, and 20% underwent no surgical intervention. Reasons for not undergoing CRS were disease-related (n = 14, 70%), due to poor performance status (n = 1, 5%), or both (n = 5, 25%). Five-year overall survival was 48.2% in KT patients who underwent CRS. Poor tumor grade was an independent predictor of mortality (hazard ratio 10.69, 95% confidence interval 1.20-95.47, P = 0.03). CONCLUSIONS: Almost 90% of our patient cohort with KTs from mCRC experience additional sites of metastasis. Around half of KT patients who underwent CRS were alive at 5 y.

Cd44v6 acts as a directional responding factor in the process of transcoelomic metastasis from gastric carcinoma to Krukenberg tumor.

INTRODUCTION: Due to the limited number of studies focusing on the optimal treatment of multiple Krukenberg tumor (KT)-gastric carcinoma (KT - GC), it is necessary to conduct large-scale studies to confirm the definite role of serum tumor markers in the diagnosis and prognosis of KT. Moreover, the clinical significance of variant 6 of CD44 (CD44v6) in transcoelomic metastasis should be considered. AREAS COVERED: This review covers molecular pre-cancer diagnosis, gastric carcinoma metastasis, and anti-cancer treatments. Additionally, gastrointestinal cancer metastasis is a key area for improvement. EXPERT OPINION: The detection of CD44v6 differs in the World Health Organization Classification of Gastric Adenocarcinoma, the Lauren Classification of Gastric Adenocarcinoma, and the anatomic location of gastric adenocarcinoma. The results were compared among the three groups. The mechanism of gastric adenocarcinoma metastasis still requires further elucidation. CD44v6 molecular detection helps clarify the pre-cancer diagnosis of KT before seeding. If subsequent studies confirm its role as a signaling molecule, it could pave the way for new research directions in clinical practice; however, additional academic confirmation is necessary.

Krukenberg Tumor Presentation of Recurrent Gallbladder Cancer After a Decade.

BACKGROUND: Krukenberg tumors are among rare cases of metastatic ovary cancers. They are presented as a solid mass which generally has bilateral and sometimes cystic components and is also known through symptoms related to the mass effect and/or hormonal imbalance. However, they may present findings before the primary tumor or remain asymptomatic for a long time. CASE REPORT: We presented a patient, who was diagnosed with gallbladder cancer nine years ago and whose adjuvant treatment was completed, applied to the outpatient clinic with the complaint of vaginal bleeding. Surgery was recommended to the patient and the patient was diagnosed with metastatic signet ring cell gallbladder cancer. The patient was started on gemcitabine-capecitabine treatment after surgery. CONCLUSION: The case is important both due to the rareness of metastasis of gall bladder cancer on the ovaries and also the detection of metastasis following the nine-year recurrence-free period. This case shows that routine controls including a careful gynecological examination in a patient primarily detected to have gastrointestinal malignity are important for recognizing late metastases.

Clinics and pathology of Krukenberg tumor: a systematic review and meta-analysis.

INTRODUCTION: Krukenberg tumor (KT) is defined as a secondary neoplasm of the ovary. While ovarian metastases account for about 30% of ovarian tumors, KTs are rare, accounting for about 1-2% of the total. The rarity of KT is at least in part responsible for the lack of a precise clinic-pathological characterization of these tumors. Clinically, KT may have a subtle clinical presentation, with few symptomatic manifestations and nonspecific clinical signs, even though in literature there is disagreement about the clinical presentation of these patients; such difficulties in the diagnostic framework often leads to a delayed diagnosis with serious consequences on the patient outcome. We aimed to provide a clinico-pathological characterization of Krukenberg Tumor (KT) through a systematic review and meta-analysis to improve the diagnosis and management of KT. EVIDENCE ACQUISITION: Electronic databases were searched for all studies assessing clinico-pathological features of KT series. Pooled prevalence of each clinical or pathological factor was calculated according to the random-effect model. EVIDENCE SYNTHESIS: Forty-eight studies with 3025 KT patients were included; 39.7% of patients were ≥50 and 39.8% were postmenopausal. The most common primary tumor sites were stomach (42.5%), colon-rectum (26.1%), breast (9.3%), and appendix (5%); 48.7% of KTs were synchronous with the primary tumor, 64.3% were bilateral, 40.5% had a diameter ≥10 cm; 55.3% showed extraovarian extent and 49% showed peritoneal involvement. The most common presenting symptoms were ascites (51.7%), palpable mass (31.3%), pain (29.3%), abdominal distention (28.7%), irregular bleeding (9.1%), asymptomatic (11.2%). CONCLUSIONS: KT shows a highly variable presentation. Understanding the prevalence of clinico-pathological factors may be helpful to improve the diagnosis and management of KT.

Krukenberg Tumor of Ovary During Pregnancy: Learning From A Mistake.

Sertoli-Leydig cell tumor of the ovary with heterologous differentiation is a relatively uncommon tumor that occurs in females of variable age range. Krukenberg tumor (KT) is a relatively more common tumor of the ovary although only a few cases of KT occur during pregnancy making it an equally uncommon tumor in this setting. We received a unilateral ovarian mass in a 25-yr-old primigravida which we reported as Sertoli-Leydig cell tumor with heterologous (intestinal) differentiation based on its clinical and histomorphologic features. However, on further investigation, a gastric mass was found which was a signet-ring cell adenocarcinoma. We rectified our diagnosis of ovarian mass as KT. We retrospectively analyzed the reasons for our mistake and concluded that the rarity coupled with the nonclassic clinical features and histomorphology of KT during pregnancy pose challenges to the correct diagnosis. This report highlights the diagnostic challenges faced by us along with the ways to circumvent them in the future.

A Rare Malignity of Childhood: Krukenberg Tumor-Case Report and Review of Literature.

Krukenberg tumor (KT) is a rare ovarian carcinoma containing mucin-filled signet ring cells. It accounts for 1%-2% of all ovarian tumors. It is seen at an average age of 40 years. Reported pediatric cases of KT in the literature are very limited. Herein, we present an adolescent with a KT that was compatible with metastatic ring cell colon carcinoma.

[Diagnosis and treatment strategy of gastric cancer with ovarian metastasis].

Ovary is one of the common metastatic sites of gastric cancer. In the female patients, ovarian relapse is one of the most important causes of treatment failure for gastric cancer. The most likely mechanism of Krukenberg tumor development is via retrograde lymphatic spreading from gastric cancer. However, neither optimal treatment strategy nor standard treatment guideline for Krukenberg tumor from gastric cancer has been clearly established.The diagnostic key points consist of the previous or concomitant history of gastric cancer and the detection of ovarian solid tumors.The therapeutic regimens mainly include the metastasectomy, chemotherapy, radiotherapy and comprehensive treatment. Surgical resection of metastatic tumor combined with adjuvant chemotherapy can improve the prognosis and survival.

[Krukenberg tumour: about 5 cases]. / Tumeur de Krukenberg: à propos de 5 cas.

Krukenberg tumours are rare, often bilateral ovarian malignant tumours secondary to muco-secreting gastric cancer, in 90% of cases. We collected data from patients' medical records over a period of 17years, between January 2002 and January 2019. These patients had Krukenberg tumors for which they were treated in the Department of Hepato-Gastro-Enterology at the Ibn Rochd Hospital University. The purpose of this retrospective, descriptive study was to update the current understanding of this type of neoplasm characterized by poor prognosis, in order to improve diagnostic performance and therapeutic treatment. The average age of our patients was 42 years, ranging between 25 and 61 years. Ascites was the most common manifestation and was reported in 80% of cases. Radiological assessment highlighted ovarian tumor of variable size and echo structure, unilateral in 60% of cases. Oeso-gastroduodenal fibroscopy showed gastric process in 4 patients. Surgical exploration and immunohistochemical examination of biopsic specimens resulted in the correct diagnosis of cancer of the transverse colon with massive locoregional extension and gastric infiltration in one case. The fifth patient underwent exploratory laparotomy which revealed metastatic colonic neoplasia. Radical surgery could be performed only in two patients, in the other two cases only biopsies were performed due to the late stage of the disease. One patient had profoundly altered general state and was at high-risk for anaesthetic, then surgical procedure could not be performed. Only two patients received postoperative chemotherapy. Fatal outcome was reported in 100% of cases. This study reconfirms the catastrophic prognosis of Krukenberg tumor based on its insidious evolution often leading to late diagnosis and to a clear misunderstanding of its etiopathogenesis. We conclude that the improvement of survival chances is based on systematic assessment of ovaries in patients with digestive neoplasia. Some authors also affirm that prophylactic ovariectomy should be performed in women older than 40 years who have undergone gastrointestinal cancer surgery.

Signet Ring Stromal Cell Tumor: A Legitimate (Benign) Mimic of Krukenberg Tumor.

Signet ring stromal cell tumor is a rare, benign ovarian neoplasm thought to arise from ovarian stromal cells. The pathophysiology of these tumors is poorly understood. They present in women in a wide age range, often with nonspecific symptoms including lower abdominal or pelvic pain. Their morphologic appearance raises a critical differential diagnosis of Krukenberg tumor, an aggressive malignancy with significant implications for patient management. For this reason, it is important for the pathologist to be aware of signet ring stromal cell tumor and its differentiating features, including useful histochemical and immunohistochemical ancillary tests. These tumors are curable with surgical excision, and there have been no recurrences or metastases among reported cases.

Malignant phyllodes tumor metastatic to bilateral ovaries: A Krukenberg-like presentation.

Phyllodes tumor (PT) is an extremely rare tumor of the breast of mixed mesenchymal and epithelial origin. It may pursue a benign or malignant evolution with distant metastases in the latter case in 3-12% of patients. The most common sites of metastases are the lungs and bones. Although theoretically any organ may have metastasis, it is extremely rare that a PT will metastasize to the bilateral ovaries and present as Krukenberg tumor. Herein, we report such a case.

PD-L1 Expression Predicts a Distinct Prognosis in Krukenberg Tumor with Corresponding Origins.

Krukenberg tumor (KT) is an uncommon ovarian metastatic signet-ring cell adenocarcinoma that mostly metastasizes from gastrointestinal carcinoma. Optimal treatment options for KTs are limited. Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have shown remarkable activity in clinical trials for metastatic tumors. Here, we evaluated PD-L1 expression and T cell infiltration in KTs and their corresponding primary tumors. Positive tumor PD-L1 expression was detected in 9 (25.7%) KTs from gastric carcinomas (GCs) and in 20 (66.7%) KTs from colorectal carcinomas (CRCs). Patient survival was assessed according to the PD-L1 status and CD8+ T cell density. Positive tumor PD-L1 expression in KTs from GCs was associated with poor prognosis. In contrast, positive tumor PD-L1 expression in KTs from CRCs was associated with an improved prognosis. We analyzed copy number variations of the PD-L1 gene in KTs. PD-L1 expression was higher in cases with copy number gains. The T cell densities within KTs and their corresponding primary tumors were compared. The densities of CD8+ T cells correlated significantly between the primary tumors and KTs from the same case. Taken together, the research further highlighted targets for immune-based therapy in KTs from GCs and CRCs.

Pressurized intraperitoneal aerosol chemotheprapy after misdiagnosed gastric cancer: Case report and review of the literature.

We report the first application of pressurized intraperitoneal aerosol chemotherapy (PIPAC) as a rescue therapy before palliative D2 gastrectomy combined with liver metastasectomy performed in a 49-year-old woman with peritoneal carcinomatosis who was primarily diagnosed with and underwent surgery for a Krukenberg tumor. The PIPAC procedure was performed with the use of cisplatin at 7.5 mg/m2 and doxorubicin at 1.5 mg/m2 for 30 min at 37 °C. Eight weeks after the PIPAC procedure, the patient underwent open classic D2 gastrectomy with the creation of a Roux-en-Y anastomosis (RNY) combined with liver metastasectomy. The patient underwent the classic protocol for chemotherapy combined with Xeloda. The patient felt better and returned to her daily activities. Multicenter data should be gathered to confirm the usefulness of PIPAC as a rescue or neoadjuvant supportive therapy in a very select group of patients who have been recently qualified to undergo classic chemotherapy or standard oncologic surgical procedures.

A rare Krukenberg tumor arising from a primary adenocarcinoma of the small intestine.

OBJECTIVE: A Krukenberg tumor is a malignancy in the ovary that metastasizes from a primary site. Here, we report a very rare case of bilateral Krukenberg tumors of the ovaries arising from a primary adenocarcinoma of the small intestine in a 53-year-old Taiwanese woman. CASE REPORT: The patient presented with a 3-month history of abdominal distension and acid regurgitation. Gastroscopy and colonoscopy findings were negative. According to the preoperative image, we highly suspected that the small bowel mass was the primary tumor with metastatic tumors to bilateral ovarian masses. The diagnosis was made immediately after operation. Results from pathology and immunohistochemical report confirmed our diagnosis. CONCLUSION: The primary lesion of a Krukenberg tumor is generally too small to be detected. Thus, careful radiographic and endoscopic exploration of the digestive system is necessary to detect the primary tumor. Immunohistochemical evaluation is also useful for determining the primary site of the adenocarcinoma.

Immunohistochemical diagnosis of Krukenberg tumors.

The diagnosis of Krukenberg tumors, as in other types of metastatic tumors of unknown primary origin, can often be a challenge for clinicians. In many cases, traditional diagnostic methods are insufficient, requiring immunohistochemistry analysis for identifying the origin of metastatic tumors. In our study, we examined a total of 34 female patients with Krukenberg tumors with different sites of the primary tumor: gastric (n=18), colorectal (n=6) or breast (n=7) and tumors with unknown origin (n=3). Cytokeratin (CK) 7 and CK20, carcinoembryonic antigen (CEA) and cancer antigen (CA) 125 were applied. The analysis of immunohistochemical profiles for CEA and CA125 showed that, regardless of the histological origin, the predominant immunohistochemical profile was CEA(+)÷CA125(-). CK7÷CK20 profile was different depending on the histological origin of the Krukenberg tumors. Thus, for the cases of gastric origin, CK7(-)÷CK20(-) was present in 66.7% (12÷18) of the cases. For the cases with colorectal origin, the predominant immunohistochemical profile was CK7(-)÷CK20(+), in a percentage of 66.7% (4÷6). The combination CK7(+)÷CK20(-) was found in 85.7% (6÷7) among cases of breast origin. Consequently, the immunohistochemical profile CK7÷CK20 can have a key role in identifying the primary tumor in patients with Krukenberg tumors of unknown origin.

Pregnancy With Bilateral Metastatic Ovarian Tumour.

Metastatic ovarian tumours are extremely rare. The commonest primary site is usually stomach and the metastasis from this site is termed as krukenberg tumour. It accounts for 1-2% of malignant ovarian tumours. We present a case of 14 weeks' pregnancy with metastatic bilateral malignant ovarian tumour is presented. Diagnosis was made on ultrasound. Tumour markers were insignificant. Patient underwent staging laparotomy with total abdominal hysterectomy and bilateral salpingo oophorectomy and partial omentectomy. She also had haematemesis. Endoscopy revealed suspicious growth in stomach, but biopsy report excluded it. Case was handed over to the oncologist for further management.

Unexpected obstetric haemorrhage. Krukenberg tumour. / Hemorragia obstétrica de causa inesperada. Tumor de Krukenberg.

Obstetric haemorrhage can endanger the lives of mother and foetus. It often occurs unexpectedly without clear predictors. A high degree of suspicion helps to avoid delaying resuscitation measures. We present the case of a ruptured ovarian metastasis that occurred during labour. It caused a massive bleed forcing a caesarean section due to non-reassuring foetal status. This was an unprecedented and undescribed onset of Krukenberg tumour formation. Malignant tumours in pregnancy are rare and difficult to diagnose due to their clinical manifestations which often overlap with those of pregnancy itself (dyspepsia, nausea and bloating). Despite the available therapeutic measures, a delay in diagnosis is a determining factor for long-term prognosis. We review the causes of obstetric bleeding, and underline how rare Krukenberg tumours concomitant to pregnancy are.

The Application Value of HNF-1ß Transcription Factor in the Diagnosis of Ovarian Clear Cell Carcinoma.

The purpose of this study was to investigate the expression of HNF-1ß in various types of epithelial ovarian cancers and to discuss its utilization in the diagnosis of ovarian clear cell carcinoma (OCCC). This study was designed to detect HNF-1ß proteins in 27 OCCCs, 35 high-grade serous carcinomas, 21 endometrioid adenocarcinomas, 10 mucinous carcinomas, 2 transitional cell carcinomas, and 13 metastatic Krukenberg tumors by EnVision immunohistochemical system. Twenty-three of 27 (85.2%) OCCCs showed diffuse moderate to strong nuclear staining for HNF-1ß. In the 35 high-grade serous ovarian cancers, HNF-1ß was detected in 1 (2.9%) case. Five of 21 (23.8%) ovarian endometrioid adenocarcinomas were positive for HNF-1ß. Six cases of ovarian mucinous carcinomas displayed diffused moderate to strong nuclear HNF-1ß expression, yielding a positive rate of 60%. In the 13 Krukenberg tumors, HNF-1ß was detected in 7 cases with a positive rate of 53.8% and both ovary transitional cell carcinomas were negative for HNF-1ß transcription factor. Compared with HNF1ß expression in OCCCs, serous carcinomas and endometrial adenocarcinomas were significantly lower (P<0.01). However, HNF1ß expression in mucinous carcinomas and Krukenberg tumors were not significantly different from the expression in OCCCs (P>0.05). Using HNF-1ß as a diagnostic tool for OCCC showed a sensitivity and specificity of 85.2% and 76.5%, respectively. HNF-1ß can serve as an OCCC marker with a relatively high sensitivity. The diffuse and strong HNF-1ß expression pattern can be used to diagnose OCCCs with high specificity.