Secondary tumors of the ovary account for 10–25% of all ovarian malignancies. The most common tumors that give rise to ovarian metastases include breast, colorectal, endometrial, stomach, and appendix cancer. The correct diagnosis of secondary ovarian tumors may be challenging as they are not infrequently misdiagnosed as primary ovarian cancer, particularly in the case of mucinous adenocarcinomas. The distinction from the latter is essential, as it requires different treatment. Immunohistochemistry plays an important role in distinguishing primary ovarian tumors from extra-ovarian metastases and, furthermore, may suggest the primary tumor site. Despite extensive study, some cases remain equivocal even after assessing a broad spectrum of antigens. Therefore, gene expression profiling represents an approach able to further discriminate equivocal findings, and one that has been proven effective in determining the origin of cancer of unknown primary site. The available data concerning secondary ovarian tumors is rather limited owing to the relative heterogeneity of this group and the practical absence of any prospective trials. However, several intriguing questions are encountered in daily practice, including rational diagnostic workup, the role of cytoreductive surgery, and consequent adjuvant chemotherapy. This review seeks to address these issues comprehensively and summarize current knowledge on the epidemiology, pathogenesis, and management of secondary ovarian tumors, including further discussion on the different pathways of metastatisation, metastatic organotropism, and their possible molecular mechanisms.

BackgroundGreat progress has recently been made in the treatment of metastatic renal cell carcinoma, including the introduction of nivolumab, an immune checkpoint inhibitor. Despite promising results, this treatment brings a completely new spectrum of adverse events, distinct from those experienced with small-molecule kinase inhibitors. Neurologic immune-related adverse events may be serious and potentially life-threatening complications requiring immediate immunosuppressive therapy. Only a few cases of immune-related encephalitis induced by checkpoint inhibitors have been described and the data regarding the management of this serious adverse event are limited.Case presentationWe report the case of a 63-year-old white man with metastatic renal cancer who developed severe chorea-like dyskinesia during nivolumab therapy. The findings on brain magnetic resonance imaging and flow cytometry of cerebrospinal fluid, and the positivity of anti-paraneoplastic antigen Ma2 immunoglobuline G class autoantibodies were consistent with a diagnosis of immune-related encephalitis. High-dose intravenous corticosteroid therapy was started immediately, with no signs of improvement, even when infliximab was added. Our patient refused further hospitalization and was discharged. Three weeks later, he presented with signs of severe urosepsis. Despite intensive treatment, he died 4 days after admission.ConclusionsThe management of less frequent immune-related adverse events has not been fully established and more information is required to provide uniform recommendations. Immune-related encephalitis is a severe and potentially fatal complication requiring immediate hospital admission and extensive immunosuppressive therapy. The examination of cerebrospinal fluid for paraneoplastic antibodies, such as anti-N-methyl-D-aspartate receptor and anti-Ma2 antibodies, in order to distinguish autoimmune etiology from other possible causes is essential and highly recommended.Electronic supplementary materialThe online version of this article (10.1186/s13256-018-1786-9) contains supplementary material, which is available to authorized users.

Colorectal cancer (CRC) remains a serious health problem worldwide. Approximately half of patients will develop distant metastasis after CRC resection, usually with very poor prognosis afterwards. Because patient performance after distant metastasis surgery remains very heterogeneous, ranging from death within 2 years to a long-term cure, there is a clinical need for a precise risk stratification of patients to aid pre- and post-operative decisions. Furthermore, around 20% of identified CRC cases are at IV stage disease, known as a metastatic CRC (mCRC). In this review, we overview possible molecular and clinicopathological biomarkers that may provide prognostic and predictive information for patients with distant metastasis. These may comprise sidedness of the tumor, molecular profile and epigenetic characteristics of the primary tumor and arising metastatic CRC, and early markers reflecting cancer cell resistance in mCRC and biomarkers identified from transcriptome. This review discusses current stage in employment of these biomarkers in clinical practice as well as summarizes current experience in identifying predictive biomarkers in mCRC treatment.

Microsatellite instability (MSI) and mismatch repair deficiency are an emerging issue in oncology and molecular pathology. Besides being associated with better clinical outcome in colon cancer, MSI also harbors the potential to predict response to chemotherapy and immunotherapy. MSI was also observed in other solid tumors, including endometrial cancer, ovarian cancer, and melanoma, besides colon cancer. Strong evidence shows that MSI is a frequent event in melanoma. However, the data on MSI prevalence, pathogenesis, and clinical consequences in melanoma are limited. Therefore, we summarize the current knowledge on MSI in melanoma and outline future perspectives and clinical implications, including its role as a prognostic and/or a predictive factor.

Recently, new drugs targeting the immune system have been introduced to the standard care of metastatic malignant melanoma. One of these immunomodulatory drugs is ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4. The following case reports on a 54-year-old man with metastatic melanoma, who developed Grade 4 thrombocytopenia during treatment with ipilimumab already after first dose. Bone marrow examination confirmed a diagnosis of drug-induced, immune-mediated thrombocytopenia. Isolated thrombocytopenia has rarely been associated with ipilimumab and there is no standard treatment algorithm of such complication. This case demonstrates the importance of monitoring full blood count in all patients receiving ipilimumab and suggests a possible treatment algorithm.

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BackgroundDermatomyositis is an autoimmune myopathy characterized by proximal muscle weakness, muscle inflammation, and typical skin findings. It is a rare disease with an incidence of ~1/100 000. About 15–30 % of adult-onset cases are caused by underlying malignancy and dermatomyositis can be the first symptom of undiagnosed cancer, mainly in the case of anti-transcription intermediary factor 1γ (anti-TIF-1γ) antibodies presence. TIF-1γ is a transcriptional cofactor which is implicated in TGFβ signaling pathway that controls cell proliferation, differentiation, apoptosis, and tumorigenesis. Its expression was shown to be associated with younger age, higher tumor grade, more estrogen receptor negativity, tumors larger than 2 cm, and tendency towards poor outcome in early breast cancer. No association between anti-TIF-1γ antibodies and prognosis has been proposed yet.Case presentationWe report a case of a 43-year-old premenopausal woman presenting with the symptoms of systemic rheumatic disease, the most prominent being a typical skin rash and muscle pain. After a series of investigations, the patient was diagnosed with anti-TIF-1γ positive dermatomyositis and concurrent triple-negative breast cancer (cT1c N3c M0) as an underlying cause. Immediate intravenous corticosteroid therapy relieved the symptoms and enabled anticancer therapy to be commenced. Considering the tumor stage, neoadjuvant therapy with 4 courses of AC (Doxorubicin/Cyclophosphamide) followed by 4 courses of Paclitaxel/Carboplatin was administered. However, no tumor regression was documented and radiotherapy was chosen as the definitive treatment.ConclusionEarly detection of anti-TIF-1γ autoantibodies can contribute to a rapid diagnosis of tumor-associated dermatomyositis and enable immediate anticancer treatment. We demonstrate the emerging role of anti-TIF-1γ antibodies in the diagnostics of tumor-associated dermatomyositis. Furthermore, we propose a potential role of anti-TIF-1γ antibodies as a prognostic marker in early breast cancer patients.

Background: The use of nivolumab in the treatment of metastatic melanoma has become well established dur ing past years. Despite its undeniable efficacy, immune-related side effects may occur, includ ing acute liver injury. Liver toxicity caused by nivolumab is usually observed as liver enzyme elevation with mild or no symp toms; further, there is limited information regard ing any histopathological findings. Case: We report a case of a 38-year-old woman with metastatic melanoma who developed unusual nivolumab-induced hepatic injury after a single dose of nivolumab. A liver bio psy was performed to assess the aetiology of hepatic lesions as no other analysis concern ing bio chemistry, virology, autoantibodies, nor imag ing studies revealed any pathology. The histopathological analysis showed an oedema in the portal fields and mixed inflammation consist ing of eosinophilic and neutrophilic granulocytes. The major find ing was a prominent, predominantly intracellular, cholestasis. Conclusion: To our knowledge, no such histopathological pattern of liver injury has been described in relation to nivolumab ther apy elsewhere. This type of liver injury shows higher resistance to corticosteroids, which may warrant upfront high-dose corticother apy combined with other immunosuppressive agents, includ ing mycophenolate mofetil. This case highlights a necessary awareness regard ing immunotherapy-related adverse events, which could be severe and potentially life-threatening.