Synchronous skull base and spinal metastases in a patient with treatment-resistant, high-grade serous adenocarcinoma of tubo-ovarian origin.

Brain metastases (BMs) arising from ovarian cancer remain rare. Spinal cord metastases are even rarer, accounting for just 0.4% of total metastatic spinal cord compressions. In this report, we describe a case of a woman in her 70s who developed sequential brain and spinal cord metastases during her treatment for high-grade serous ovarian cancer, without a germline or somatic BRCA mutation. Following completion of neoadjuvant chemotherapy, interval debulking surgery and adjuvant chemotherapy, relapsed disease was ultimately identified as a single BM, curiously mimicking an acoustic neuroma. Subsequently, spinal cord metastases rapidly developed. Throughout, multidisciplinary team meetings guided decisions on patient management. In this report, we highlight the rarity of such a presentation and discuss the possible role of disease pathophysiology, associated systemic anticancer therapy resistance, and treatment possibilities for both cerebral and spinal metastases.

First Reported Histologically and Molecularly Confirmed Bilateral High-Grade Serous Ovarian Adenocarcinoma Metastasized to Placental Decidua of the Membranes.

A 43-year-old female presented with blood loss and persistent abdominal pain at 14 weeks of gestation. Ultrasound examination and subsequent magnetic resonance imaging (MRI) revealed bilateral multicystic uterine adnexa. Exploratory laparotomy was performed at 17 weeks of gestation and bilateral serous ovarian adenocarcinoma FIGO stage IIIC was diagnosed. Complete cytoreductive surgery (CRS) was not feasible at that moment. Nine days after the exploratory laparotomy, immature rupture of membranes and contractions occurred and she delivered a premature boy after 19 weeks of gestation. Pathological examination of the placenta revealed that her ovarian cancer metastasized to the membranes. We describe the first case of ovarian cancer metastasized to the decidua of the placental membranes with histological, immunohistochemical, and molecular confirmation. This case highlights the importance of conscientious evaluation of placenta and membranes in pregnant women with ovarian cancer.

Unusual presentation of jejunal adenocarcinoma and ovarian metastasis.

It is rare to find a small bowel tumour presenting as intestinal obstruction. This type of cancer is an extremely unusual condition often misdiagnosed until late stages. We report the case of a patient with persistent vomiting secondary to an obstructing jejunal adenocarcinoma not related to intestinal bowel disease. After resection and chemotherapy treatment a huge mass was detected in the left ovary. The anatomopathological findings confirmed a metastatic cancer consequent to the jejunal adenocarcinoma previously resected. This case illustrates a successful outcome of a jejunal adenocarcinoma with very poor prognosis after a extremely unusual ovarian metastasis. It is highly important to suspect other causes than intestinal bowel disease when doing a differential diagnosis in a young patient presenting with clinical symptoms of intestinal obstruction.

Pattern A endocervical adenocarcinomas with ovarian metastasis are indolent and molecularly distinct from destructively invasive adenocarcinomas.

AIMS: The invasive pattern in HPV-associated endocervical adenocarcinoma (HPVA) has prognostic value. Non-destructive (pattern A) HPVA has excellent prognosis mirroring adenocarcinoma in-situ (AIS). However, the rare occurrence of ovarian spread in these tumours suggests aggressiveness in a subset of patients with these otherwise indolent lesions. We hypothesise that AIS/pattern A HPVA with ovarian metastases are biologically different than metastatic destructively invasive HPVA. METHODS AND RESULTS: Samples from patients with HPVA and synchronous or metachronous metastases were retrieved and reviewed to confirm diagnosis and determine the Silva pattern in the primary lesion. For each case, normal tissue, cervical tumour and at least one metastasis underwent comprehensive sequencing using a 447-gene panel. Pathogenic single-nucleotide variants and segmental copy-number alterations (CNA), tumour mutational burden and molecular signatures were evaluated and compared between primary and metastases and among invasive pattern categories. We identified 13 patients: four had AIS/pattern A primaries, while nine had pattern B/C tumours. All AIS/pattern A lesions had metastasis only to ovary; 50% of patients with ovarian involvement, regardless of invasive pattern, also had involvement of the endometrium and/or fallopian tube mucosa by HPVA. In the ovary, AIS/pattern A HPVA showed deceptive well-differentiated glands, often with adenofibroma-like appearance. Conversely, pattern C HPVAs consistently showed overt infiltrative features in the ovary. Sequencing confirmed the genetic relationship between primary and metastatic tumours in each case. PIK3CA alterations were identified in three of four AIS/pattern A HPVAs and three of eight pattern B/C tumours with sequenced metastases. Pattern C tumours showed a notably higher number of CNA in primary tumours compared to pattern A/B tumours. Only one metastatic AIS/pattern A HPVA had a novel pathogenic variant compared to the primary. Conversely, five of eight pattern B/C tumours with sequenced metastases developed novel pathogenic variants in the metastasis not seen in the primary. All four AIS/pattern A patients were alive and free of disease at 31, 47, 58 and 212 months after initial diagnosis. Conversely, cancer-related death was documented in five of nine pattern B/C patients with follow-up at 7, 20, 20, 43 and 87 months. CONCLUSION: Morphologically and genomically, AIS/pattern A HPVA with secondary ovarian involvement appears distinct from destructively invasive tumours. In at least a subset of these cases, ovarian spread appears to occur via trans-Mullerian superficial extension, different from the stromal and lymphatic vascular spread typical of more aggressive tumours (pattern C). These differences may explain the indolent outcome observed in the rare subset of patients with AIS/pattern A HPVA and ovarian metastasis. Our data underscore the potential for conservative surgical management approaches to pattern A HPVA.

Effect of metastasectomy on the outcome of patients with ovarian metastasis of colorectal cancer: A systematic review and meta-analysis.

PURPOSE: Patients with ovarian metastasis of colorectal cancer (CROM) usually have poor prognosis. Metastasectomy is controversial in patients with CROM. This study aims to evaluate the prognostic value of ovarian metastasectomy and other factors in CROM patients. METHODS: We searched literature up to November 1, 2021 in MEDLINE (PubMed), Embase, Cochrane Library, and Clinicaltrials.gov. Retrospective studies were assessed if survival outcome of CROM patients was reported. Results were pooled in a random-effects model and reported as hazard ratios (HRs) with 95% confidence intervals (CI). Sensitivity was analyzed. RESULTS: Among 2497 studies screened, 15 studies with 997 patients, published between 2000 and 2021, were included. Longer overall survival (OS) was correlated with ovarian metastasectomy (pooled HR = 0.44, 95% CI: 0.34-0.58, P < 0.05) and R0 resection (pooled HR = 0.26, 95% CI: 0.16-0.41, P < 0.05). Longer disease-specific survival (DSS) was associated with systematic chemotherapy (pooled HR = 0.26, 95% CI: 0.15-0.45, P < 0.0001). Shorter OS was associated with extraovarian metastases (pooled HR = 3.00, 95% CI 1.68-5.36, P < 0.05) and bilateral OM (pooled HR = 1.66, 95% CI: 1.09-2.51, P < 0.05). No significant difference in OS was observed among patients with systematic chemotherapy (pooled HR = 0.68, 95% CI: 0.35-1.31, P > 0.05). CONCLUSION: Metastasectomy achieving R0 resection can significantly prolong OS and DSS of CROM patients as a reasonable treatment modality. Primary tumor resection and systematic chemotherapy can improve patients' outcomes. REGISTRATION NUMBER: CRD42022299185 (http://www.crd.york.ac.uk/PROSPERO).

Functional neuronal circuits promote disease progression in cancer.

The molecular and functional contributions of intratumoral nerves to disease remain largely unknown. We localized synaptic markers within tumors suggesting that these nerves form functional connections. Consistent with this, electrophysiological analysis shows that malignancies harbor significantly higher electrical activity than benign disease or normal tissues. We also demonstrate pharmacologic silencing of tumoral electrical activity. Tumors implanted in transgenic animals lacking nociceptor neurons show reduced electrical activity. These data suggest that intratumoral nerves remain functional at the tumor bed. Immunohistochemical staining demonstrates the presence of the neuropeptide, Substance P (SP), within the tumor space. We show that tumor cells express the SP receptor, NK1R, and that ligand/receptor engagement promotes cellular proliferation and migration. Our findings identify a mechanism whereby intratumoral nerves promote cancer progression.

Prediction of high-risk factors for ovarian metastasis in patients with endometrial cancer: A large-sample retrospective case-control study.

OBJECTIVE: To determine the high-risk factors of ovarian metastasis of endometrial cancer and their impact on prognosis. METHODS: A retrospective case-control study was conducted on a large cohort of patients with endometrial cancer. RESULTS: A total of 1240 patients with endometrial cancer were eligible for analysis, of whom 120 (9.7%) had ovarian metastasis. The patients with endometrial cancer with ovarian metastasis were more likely to have deep myometrial infiltration, lymph node metastasis, and elevated levels of CA125. The median survival was 39 months in patients with ovarian metastasis and 111 months in those without ovarian metastasis (P < 0.001). According to the stratified analysis, the progression-free survival (PFS) and overall survival in the low-risk group and PFS in the high-risk group of patients with endometrial cancer with ovarian metastasis were significantly shorter than those without ovarian metastasis (P < 0.0001, P = 0.0034, and P < 0.0001, respectively). CONCLUSION: Deep myometrial invasion, lymph node metastasis, and elevated levels of CA125 may be independent high-risk factors for ovarian metastasis in patients with endometrial cancer. Ovarian metastasis has a greater impact on the prognosis of patients with low-risk endometrial cancer.

[Laparoscopic Resection of a Liver and Ovarian Metastasis of Transverse Colon Cancer-A Case Report].

A 60s woman was diagnosed to transverse colon cancer and she underwent laparoscopic right hemicolectomy. Localized peritoneal dissemination surrounding tumor was detected during surgery. She was administrated to chemotherapy due to a hepatic metastasis in S2/3 postoperatively. Subsequently, PET-CT revealed a left ovarian metastasis in addition to a liver metastasis during chemotherapy. Laparoscopic hepatic left lateral segmentectomy and bilateral adnexectomy was performed at 1 year and 9 months after the first surgery and histopathological examination showed a metastasis of transverse colon cancer. The growth of liver and lung metastases and peritoneal disseminations was detected at 6 months later after the second surgery and the patient is currently receiving palliative treatment. Previous literatures described that ovarian metastasis of colon cancer showed bilateral metastasis and resistance to chemotherapy frequently and ruptured in some cases. We should consider to resect bilateral ovary even if unilateral metastasis alone was detected by imaging examination.

Stage IA1 HPV-associated cervical squamous cell carcinoma metastasizing to ovary by special pathway: a case report and literature review.

BACKGROUND: As the leading cancer of the female reproductive tract, it is not uncommon for human papilloma virus (HPV)-associated cervical squamous cell carcinoma (HPV-CSCC) to metastasize to pelvic organs and lymph nodes in advanced stages. However, herein, we present a rare case in which superficial invasive HPV-CSCC metastasized to the unilateral ovary as a large mass by spreading directly through the endometrium and fallopian tubes and lymph-vascular space invasion. The case is so unexpected that the misdiagnosis most likely could be proceeded as a primary ovarian cancer. CASE PRESENTATION: A 58-year-old postmenopausal woman presented vaginal bleeding for more than 4 months, never received hormonal treatment and had no family history of malignant diseases. Routine ultrasound revealed a 12 × 10 × 10 cm right ovarian mass. Intraoperative frozen section was diagnosed as a borderline Brenner tumour with local highly suspected invasive carcinoma. Accordingly, omentectomy surgery then occurred. Unbelievably, by observation under a microscope, immunohistochemistrial staining, and HPV RNA scope, we found that the carcinoma originated from the uterine cervix. In the uterine cervix, stage IA1 superficial invasive squamous carcinoma was found, and the carcinoma directly spread to the endometrium and bilateral fallopian tube, was planted into the right ovary and eventually grew as a large mass. Moreover, lymph-vascular space invasion (LVSI) was also discovered. To date, the patient has been given 6 cycles of chemotherapy and has experienced no recurrence. CONCLUSIONS: The diagnosis of superficial invasive cervical squamous cell carcinoma metastasizing to the ovary is very challenging for pathological doctors, especially in intraoperative consultations.

Seeing the whole picture: Added value of MRI for extraperitoneal findings in CRS-HIPEC candidates.

PURPOSE: In colorectal cancer (CRC) patients the selection of suitable cytoreductive surgery and hyperthermic peritoneal chemotherapy (CRS-HIPEC) candidates is based on the location and extent of peritoneal metastases (PM) and presence of extraperitoneal metastases. MRI is increasingly being used to accurately assess the extent of PM, however, the significance of extraperitoneal findings in these scans has never been evaluated before. METHODS: CRC patients who had undergone an additional MRI scan after standard work-up with CT for preoperative staging between January 2016-January 2020 were selected. CT and MRI reports were reviewed for new abdominopelvic extra-peritoneal findings on MRI (MR-EPF) and MR-EPFs concerning lesions previously indicated as equivocal (uncertain benign/malignant) on CT. Reference standard were surgical results or follow-up imaging. RESULTS: In 158 included patients 60 MR-EPFs (in 58/158 patients) were noted: twenty-six (43%) were new findings and thirty-four (57%) were equivocal findings on CT. Of the 34 equivocal findings 27 were 'rejected/less likely malignant' and 7 'confirmed/more likely malignant' based on MRI. In 29 patients (18%) the MR-EPFs had direct influence on treatment planning. Three patients (2%), eligible for CRS-HIPEC on CT, were deemed inoperable due to MR-EPFs. CONCLUSION: MRI had an added value in more than a third of the patients due to abdominopelvic extraperitoneal findings that were undetected or indeterminate on CT and therefore influenced the treatment in a substantial part of the patients. Combined with the known accurate detection of peritoneal disease on MRI, MRI seems a logical addition to the diagnostic workup of potential CRS-HIPEC candidates.

Lobular Carcinoma of the Breast Metastatic to the Ovary: A Clinicopathologic Study of 38 Cases.

We evaluated the clinicopathologic features of 38 cases of metastatic lobular (n=33) or predominantly lobular (n=5) carcinoma involving the ovary. The patients were from 39 to 91 years of age (mean: 53 y). In 2 cases, the breast primary and ovarian metastasis were diagnosed synchronously, and in 5, the breast primary was only discovered after the metastatic carcinoma in the ovary was found. In the majority of cases (79%), both ovaries were involved; the mean ovarian tumor size was 5.9 cm. The ovarian tumors demonstrated a range of architectural patterns including macronodular (71%), diffuse/solid growth (87%), single-cell infiltration (87%), cords (74%), and small nests/clusters (50%). Nine cases demonstrated focal signet ring cell morphology. The associated stromal reaction ranged from none to marked, with almost half of cases demonstrating a marked stromal response, largely prominent sclerosis. A variety of neoplasms, most typically sex cord-stromal tumors, lymphoma/leukemia, and desmoplastic small round cell tumor, may enter the differential. In addition to the obvious help afforded in most cases by the clinical history, a combination of judicious sampling, particularly to unearth the delicate cords or single-cell growth of lobular carcinoma, appropriate consideration of the cytologic features of the neoplastic cells, and immunohistochemistry can resolve the diverse issues in differential diagnosis that may arise.

Prognosis of poorly cohesive gastric cancer after complete cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (CYTO-CHIP study).

BACKGROUND: The incidence of gastric poorly cohesive carcinoma (PCC) is increasing. The prognosis for patients with peritoneal metastases remains poor and the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The aim was to clarify the impact of gastric PCC with peritoneal metastases treated by CRS with or without HIPEC. METHODS: All patients with peritoneal metastases from gastric cancer treated with CRS with or without HIPEC, in 19 French centres, between 1989 and 2014, were identified from institutional databases. Clinicopathological characteristics and outcomes were compared between PCC and non-PCC subtypes, and the possible benefit of HIPEC was assessed. RESULTS: In total, 277 patients were included (188 PCC, 89 non-PCC). HIPEC was performed in 180 of 277 patients (65 per cent), including 124 of 188 with PCC (66 per cent). Median overall survival (OS) was 14.7 (95 per cent c.i. 12.7 to 17.3) months in the PCC group versus 21.2 (14.7 to 36.4) months in the non-PCC group (P < 0.001). In multivariable analyses, PCC (hazard ratio (HR) 1.51, 95 per cent c.i. 1.01 to 2.25; P = 0.044) was associated with poorer OS, as were pN3, Peritoneal Cancer Index (PCI), and resection with a completeness of cytoreduction score of 1, whereas HIPEC was associated with improved OS (HR 0.52; P < 0.001). The benefit of CRS-HIPEC over CRS alone was consistent, irrespective of histology, with a median OS of 16.7 versus 11.3 months (HR 0.60, 0.39 to 0.92; P = 0.018) in the PCC group, and 34.5 versus 14.3 months (HR 0.43, 0.25 to 0.75; P = 0.003) in the non-PCC group. Non-PCC and HIPEC were independently associated with improved recurrence-free survival and fewer peritoneal recurrences. In patients who underwent HIPEC, PCI values of below 7 and less than 13 were predictive of OS in PCC and non-PCC populations respectively. CONCLUSION: In selected patients, CRS-HIPEC offers acceptable outcomes among those with gastric PCC and long survival for patients without PCC.

Bone metaplasia in ovarian metastasis of colorectal carcinoma.

Calcerrada Alises E, et al. presented the case of a hyperplastic polyp with bone metaplasia. We present the case of a patient with metastatic colorectal adenocarcinoma in the ovary, with bone metaplasia in the ovarian metastasis but not in the primary lesion.

Colorectal cancer ovarian metastases.

OBJECTIVE: Ovarian metastases occur in 3%-5% of patients with colorectal cancer. The role of oophorectomy in that setting continues to be debated. We aimed to assess the survival of women treated with metastasectomy for ovarian metastasis. METHODS: Retrospective cohort study of patients in the California Cancer Registry (2000-2012) with stage IV colorectal cancer and ovarian metastases. Pathology other than adenocarcinoma was excluded. Adjusted Cox-proportional hazard analysis was applied to assess the risk of death. RESULTS: A total of 756 patients with synchronous ovarian metastases and 516 patients with metachronous ovarian metastases form the basis of this analysis. Median follow-up for the synchronous cohort was 21 months (IQR: 8-36). Median overall survival was 23 months (IQR: 10-42). Estimated 5-year survival reached 17% and 10-year survival was 8%. There was a significant difference in unadjusted survival between patients with solitary ovarian metastasis (median overall survival: 51 months) compared with those who had both ovarian and extraovarian metastases (20 months) (log-rank test, P<0.0001). For patients with solitary ovarian metastases, the 5- and 10-year survival was 46% and 31%, respectively. Among patients with synchronous ovarian metastases, longer unadjusted survival was observed after oophorectomy (median overall survival: 24 months) compared with no oophorectomy (18 months, log-rank P=0.01). For patients with metachronous diagnoses of colorectal cancer ovarian metastasis, the median disease-free survival was 19 months. The median survival after resection of metachronous ovarian metastases was 25 months, with the survival directly related to the disease-free interval until metastasis. For patients with resected metachronous ovarian metastases, the 5- and 10-year post-metastasectomy survival was 14% and 5%, respectively. CONCLUSIONS: Patients with colorectal cancer ovarian metastasis have favorable long-term survival. Survival rates are higher if the tumor is isolated to the ovary or if metachronous to the primary cancer.

How to manage synchronous endometrial and ovarian cancer patients?

BACKGROUNDS: We aimed to evaluate the prognosis in patients with synchronous endometrial and ovarian cancer (SEOC) by comparing the differences between double primary cancer (DPC) and metastatic cancer (MC). METHODS: The medical records of 47 patients diagnosed synchronously with endometrial and ovarian cancer between January 2006 and December 2018 were retrospectively reviewed. Twenty-eight and 19 patients were diagnosed with DPC and MC, respectively. Demographics, recurrence-free survival (RFS), and 5-year overall survival (OS) were compared. The clinical factors affecting survival were evaluated using univariate and multivariate analyses. RESULTS: The demographics were not different between both groups. Endometrioid histology and the International Federation of Gynecology and Obstetrics grade were higher in the MC group than in the DPC group (42.1% vs. 10.7%; P = 0.018, P = 0.002, respectively). The ratio of post-operative adjuvant therapy was not different in both groups. Recurrence occurred in five patients with DPC and seven with MC. The difference in RFS was not significantly different (P = 0.131) but the OS was different between both groups (P = 0.020). Histology and para-aortic lymph node metastasis were associated wtih RFS in univariate analysis, but no difference was found in multivariate analysis. CONCLUSIONS: Although DPC patients had longer OS, multivariate analysis did not identify any influential factors. Focus should be placed on defining the appropriate adjuvant treatment for high-risk patients, which will improve prognosis, rather than on discriminating between DPC and MC.

Risk of ovarian recurrence after ovarian conservation in early-stage cervical cancer treated with radical surgery: A propensity match analysis.

INTRODUCTION: The primary aim of the present study was to assess the incidence of ovarian metastasis/recurrence and the survival of patients undergoing radical hysterectomy with ovarian conservation (CONSERV) versus oophorectomy (OOPHOR). Secondary aim was to assess the incidence and the characteristics of menopausal symptoms in both groups. MATERIALS AND METHODS: Retrospective, multi-center, observational cohort study including patients <50 years with clinical FIGO 2009 stage IA1-IB1/IIA1 cervical carcinoma, treated by primary surgical treatment between 02/2007 and 07/2019. One-to-one case-control matching was used to adjust the baseline prognostic characteristics in survival analysis. RESULTS: 419 patients were included. 264 in the OOPHOR (63.0%) and 155 (37.0%) in the CONSERV group. Ovarian transposition was performed in 28/155 (18.1%) patients. 1/264 (0.4%) patient had ovarian metastasis from endocervical adenocarcinoma. After propensity-matching, 310 patients were included in the survival analysis (155 per group). 5-year disease-free survival of patients undergoing CONSERV versus OOPHOR was 90.6% versus 82.2%, respectively (p = 0.028); 5-year overall survival was 94.3% versus 90.8%, respectively (p = 0.157). Two patients (1.3%) developed recurrence on the conserved ovary. CONSERV represented an independent protective factor of recurrence (HR:0.361, 95%CI 0.169-0.769; p = 0.008). 28 (20.6%) in the CONSERV group versus 116 (60.4%) in the OOPHOR group complained of menopausal symptoms during follow up (p < 0.001). HRT was prescribed to 12.0% of patients (median HRT time was 20 months). CONCLUSION: CONSERV was associated with reduced risk of recurrence and menopausal symptoms in early-stage cervical cancer. As the risk of ovarian metastasis and ovarian recurrence is relatively low, CONSERV in pre-menopausal women has to be considered.

Fascicular Sixth Nerve Palsy as a Presenting Sign of Metastatic Ovarian Carcinoma.

ABSTRACT: The most common etiology of an isolated abducens nerve palsy in an older adult with vasculopathic risk factors is presumed microvascular ischemia. Because the diagnosis of microvascular ischemia in this setting would not alter patient management, there is debate as to whether further workup is warranted under these circumstances. In this report, we describe a fascicular sixth nerve palsy as the initial presenting sign of metastatic ovarian carcinoma, and we highlight the importance of considering additional workup in select cases of isolated abducens nerve palsies.

Spontaneous subcapsular and perirenal haemorrhage with retroperitoneal haematoma in a patient with ovarian melanoma metastases.

A 47-year-old woman was admitted to our clinic for intensive pain in the left flank region. The transvaginal ultrasound showed a left adnexal solid mass with ascites. She had undergone surgical removal of skin melanoma in 2008, but in September 2019, intracardiac metastasis resulting from it had been discovered. CT performed in March 2020 had been negative for other metastases. A full abdomen ultrasound was not performed. During the night, the patient began to show signs and symptoms of hypovolaemic shock. The patient was urgently transferred to the operating room for a video laparoscopy. A vast left retroperitoneal haematoma was diagnosed along with voluminous enlargement of the left ovary. We proceeded with a left adnexectomy and blood transfusion. Subsequent contrast-enhanced CT revealed a left subcapsular, perirenal haematoma and a voluminous retroperitoneal haematoma. Kidney metastasis was also seen. The final histological diagnosis was metastatic amelanotic malignant melanoma of the ovary.