Algorithm of genetic diagnosis for patients with head and neck paraganglioma-update.

Paragangliomas are rare tumors originating from the paraventricular bodies of the autonomic nervous system located in the adrenal glands, chest, abdomen, pelvis and head and neck. Tumors of this type account for 0.5% of head and neck cancers, 0.03% of all cancers and their incidence is estimated at 1-30/100,000 per year. Head and Neck Paragangliomas (HNPGL) are localized in carotid body, tympanic cavity or jugular foramen. It is established that HNPGL may be associated with mutations of the SDH complex, with SDHD being the most prevalent. However, SDHB, SDHC and SDHAF are also potential causes. The aforementioned mutations are influenced by various risk factors, including young age, a positive family history of paraganglioma, the presence of metastases and gender The purpose of this study is to summarize the results of genetic testing performed on patients with head and neck paraganglioma and to create an up-to-date genetic diagnosis algorithm for patients with HNPGL based on previous studies published in the literature that can be used in daily practice. Several papers observed that among SDHD mutation carriers, most or all of those studied had HNPGL, and SDHB mutations were more frequently found in the presence of metastasis. Based on the results, it was concluded that there is no basis for genetic testing for VHL in patients without a positive family history. In each algorithm proposed by different authors, proposals for rational genetic diagnosis were analyzed based on the studies cited by the author and the analyses included in our paper. For the analysis of the treatment algorithms, the following were included: Martin, Mannelli, Neumann, Gupta. Subsequently, publications related to the genetic diagnosis of HNPGL were analyzed to verify the proposed algorithms in light of the latest genetic studies and to establish an updated diagnostic management scheme.

Successful Treatment of Cutaneous Squamous Cell Cancer with Cemiplimab-A Report of Two Cases Demonstrating the Management of Pseudoprogression and Adverse Events.

Background: Cutaneous squamous cell carcinoma is a common malignancy, which frequently develops in the areas exposed to the sun. Patients with locally advanced disease in the head and neck region are frequently disqualified from surgical resection and require systemic treatment. Methods: In this report, we present the clinicopathological features and treatment of two patients who received cemiplimab, a monoclonal antibody targeting programmed cell death receptor 1 (PD-1). Results: An 80-year-old female and 82-year-old male patient were admitted to the hospital for the treatment of large tumors diagnosed as squamous cell carcinomas. In both patients, surgical treatment was not recommended due to the large dimensions of the tumors. These patients qualified for systemic treatment with cemiplimab. In the first patient, immunotherapy was interrupted due to adverse events. Nevertheless, a continuous regression of the tumor was observed despite treatment cessation. The second patient experienced a pseudoprogression, which is an increase in the tumor size caused by infiltration of immune cells. The treatment significantly reduced tumor size in both patients, which highly improved their quality of life. Conclusions: Cemiplimab offers clinical benefits in patients with cutaneous squamous cell carcinoma who are ineligible for surgical treatment. Systemic treatment can significantly improve the quality of life and reduce tumor diameters.

New Opportunities in the Systemic Treatment of Hepatocellular Carcinoma-Today and Tomorrow.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Liver cirrhosis, hepatitis B, hepatitis C, and non-alcoholic fatty liver disease represent major risk factors of HCC. Multiple different treatment options are available, depending on the Barcelona Clinic Liver Cancer (BCLC) algorithm. Systemic treatment is reserved for certain patients in stages B and C, who will not benefit from regional treatment methods. In the last fifteen years, the arsenal of available therapeutics has largely expanded, which improved treatment outcomes. Nevertheless, not all patients respond to these agents and novel combinations and drugs are needed. In this review, we aim to summarize the pathway of trials investigating the safety and efficacy of targeted therapeutics and immunotherapies since the introduction of sorafenib. Furthermore, we discuss the current evidence regarding resistance mechanisms and potential novel targets in the treatment of advanced HCC.

Anaplastic lymphoma kinase inhibitors-a review of anticancer properties, clinical efficacy, and resistance mechanisms.

Fusions and mutations of anaplastic lymphoma kinase (ALK), a tyrosine kinase receptor, have been identified in several neoplastic diseases. Rearranged ALK is a driver of tumorigenesis, which activates various signaling pathway associated with proliferation and survival. To date, several agents that target and inhibit ALK have been developed. The most studied ALK-positive disease is non-small cell lung cancer, and three generations of ALK tyrosine kinase inhibitors (TKIs) have been approved for the treatment of metastatic disease. Nevertheless, the use of ALK-TKIs is associated with acquired resistance (resistance mutations, bypass signaling), which leads to disease progression and may require a substitution or introduction of other treatment agents. Understanding of the complex nature and network of resistance mutations may allow to introduce sequential and targeted therapies. In this review, we aim to summarize the efficacy and safety profile of ALK inhibitors, describe off-target anticancer effects, and discuss resistance mechanisms in the context of personalized oncology.

Small cell carcinoma with neuroendocrine differentiation of subglottic larynx- a case report.

Small cell cancer (SCC) is a neuroendocrine neoplasm, which is most frequently found in the lungs. Extrapulmonary location of SCC is rare and may involve 2.5-5% of SCCs. We present a case of a 31-year-old male patient with an extremely uncommon subglottic SCC. The patient was qualified for a radical sequential chemoradiotherapy. After treatment, patient's condition suggested complete remission. Recurrence was detected one year later, and the disease rapidly progressed, despite a second line chemotherapy. The patient died 29 months after initial diagnosis. This case aims to raise awareness on the aggressive laryngeal SCC and its good response to first line chemotherapy composed of cisplatin and etoposide, followed by radiotherapy.

New Options for Systemic Therapies in Intrahepatic Cholangiocarcinoma (iCCA).

Intrahepatic cholangiocarcinoma (iCCA) is a malignant neoplasm of the biliary tract, the incidence of which has increased in recent years. The etiopathogenesis is not fully elucidated, but the greatest association has been shown with inflammatory changes within the biliary tract. Surgical treatment is the main therapeutic modality; however, less than 30% of its are resectable at diagnosis, with the majority of patients requiring systemic treatment. Chemotherapy with capecitabine is the standard adjuvant therapy. For patients with inoperable tumors or metastatic lesions, chemotherapy alone or in combination with immunotherapy (durvalumab, pembrolizumab) is used. There is a need to provide systemic treatment in patients with progression after first-line treatment in good performance status. New therapeutic pathways for the treatment of this tumor type are still being identified with new emerging potential targets such as isocitrate dehydrogenase (IDH), fibroblast growth factor receptor 2 (FGFR2), or BRAF mutation.

Intrahepatic Cholangiocarcinoma-Where Are We Now and Where Are We Going to?

Cholangiocarcinomas (CCAs) are a heterogeneous group of malignancies originating from the biliary tract epithelium [...].

Extremely Rare Pulmonary Metastases of Skin Basal Cell Carcinoma: Report of Two Cases with Clinicopathological Features.

Basal cell carcinoma (BCC) is the most frequent human skin cancer, but metastasizing BCC (MBCC) is extremely rare, developing in approximately 0.0028% to 0.55% of BCC patients. Herein, we report two cases of pulmonary MBCC. The first one developed in a 72-year-old male who underwent surgical resection due to multiple recurrences and adjuvant radiotherapy. Immunohistochemistry showed that neoplastic cells expressed Ber-EP4, CK5/6, p63, EMA (focally), BCL-2, and CD10, but were negative for CK7, CK20, S100, estrogen and progesterone receptors, and TTF-1. The second case is a 64-year-old female treated with vismodegib. Clinicopathological features and differential diagnoses are described.

Clinicopathological Features of Intrathoracic Liposarcoma-A Systematic Review with an Illustrative Case.

BACKGROUND: Liposarcoma (LPS) is one of the most common soft-tissue sarcomas. However, intrathoracic LPS is rare, as only 1% of all LPS cases are found in the thorax. METHODS: A systematic literature review through PubMed and Embase databases was performed. Only eligible case reports and case series reporting intrathoracic LPS in adult patients were included. Kaplan-Meier curves were calculated to evaluate the survival rate of included patients based on the histological subtype of LPS. RESULTS: 123 studies reporting 197 patients were included. We added a case of a 69-year-old female patient with recurrent giant intrathoracic LPS. The primary tumor measured 15.1cm × 22.9 cm × 21.9 cm and weighed 3100 g. Six months later, the patient was admitted to the hospital with another intrathoracic tumor measuring 9.5 cm × 9 cm× 1.4 cm. The immunohistochemical studies showed expression of murine double minute 2 (MDM2) antigen in both primary and recurrent tumor cells. CONCLUSIONS: Dyspnea, chest pain, and cough were the most common symptoms reported in included studies. Overall, the 5-year survival rate was 62%. The highest survival was observed in well-differentiated LPS patients (80%) and the lowest in myxoid LPS (31%).

Chronic Lymphocytic Leukemia-Induced Humoral Immunosuppression: A Systematic Review.

Secondary immunodeficiency is observed in all patients with chronic lymphocytic leukemia (CLL) in varying degrees. The aim of the study was to review the available literature data on patients with CLL, with particular regard to the pathogenesis of the disease and the impact of humoral immunity deficiency on the clinical and therapeutic approach. A systematic literature review was carried out by two independent authors who searched PubMed databases for studies published up to January 2020. Additionally, Google Scholar was used to evaluate search results and support manual research. The search resulted in 240 articles eligible for analysis. After all criteria and filters were applied, 22 studies were finally applied to the analysis. The data analysis showed that the clinical heterogeneity of CLL patients correlates with the diversity of molecular abnormalities determining the clinical picture of the disease, the analysis of which enables setting therapeutic targets. Additionally, in improving the therapeutic method, it is worth introducing supportive therapies with the use of vaccines, antibiotics and/or immunoglobins. Moreover, humoral immunodeficiency in CLL has a strong influence on the risk of infection in patients for whom infections are a major cause of morbidity and mortality.

The Double-Edged Sword Role of Viruses in Gastric Cancer.

Due to its high morbidity and mortality, gastric cancer is a topic of a great concern throughout the world. Major ways of treatment are gastrectomy and chemotherapy, unfortunately they are not always successful. In a search for more efficient therapy strategies, viruses and their potential seem to be an important issue. On one hand, several oncogenic viruses have been noticed in the case of gastric cancer, making the positive treatment even more advantageous, but on the other, viruses exist with a potential therapeutic role in this malignancy.

Herpesviruses in Head and Neck Cancers.

Head and neck cancers arise in the mucosa lining the oral cavity, oropharynx, hypopharynx, larynx, sinonasal tract, and nasopharynx. The etiology of head and neck cancers is complex and involves many factors, including the presence of oncogenic viruses. These types of cancers are among the most common cancers in the world. Thorough knowledge of the pathogenesis of viral infections is needed to fully understand their impact on cancer development.

Quality of Life and Adherence to Therapy in Patients With Chronic Myeloid Leukemia Treated With Nilotinib as a Second-Line Therapy: A Multicenter Prospective Observational Study.

INTRODUCTION: The aim of this study was to evaluate quality of life (QOL) and adherence to the therapy in patients with chronic myeloid leukemia in chronic phase treated with nilotinib as second-line therapy. PATIENTS AND METHODS: A multicenter, prospective, observational trial with 6 time points was conducted; 177 patients were recruited in 23 centers in Poland who were treated with nilotinib as second-line therapy because of the ineffectiveness or intolerance of their previous therapy. QOL was evaluated with the standard European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire. Adherence to the therapy was assessed using the 4-item Morisky Medication Adherence Scale by patients and their physicians. RESULTS: The average QOL in patients who completed the study was significantly higher during the last visit (69.4 ± 17.4) than at the start of the study (59.1 ± 18.8; P < .001). At their first visit, 120 (83.2%) patients assessed themselves as highly compliant and 135 (93.4%) at the fifth visit. Low-compliance patients represented 3 (1.7% of the total) during visit 1; none of the patients self-assessed as low compliance since the fourth visit. At the first visit 151 (85.3%) patients were categorized by their physicians as highly compliant and 138 (96.0%) during the last 3 visits. Patients' and their physicians' assessments were significantly correlated. CONCLUSION: The QOL among patients receiving nilotinib administered as second-line therapy was very good and adherence to the treatment was high. The efficacy and safety of the drug were confirmed in the real-life setting.

Case report: rare case of infiltration of small lymphocytic B-cell lymphoma in the thyroid gland of female patient with B-cell chronic lymphocytic leukemia (CLL-B/SLL-B).

The article presents a case of 57-year-old woman with the infiltration of rare small lymphocytic B cell lymphoma in the thyroid gland. Initially, the patient was followed-up due to chronic lymphocytic B-cell leukemia diagnosed on the basis of histopathological examination of cervical lymph node. Eight months later, general symptoms occurred along with lymphocytosis and exacerbation of lesions in lymph nodes, and therefore, chemotherapy was started according to COP regimen. After four chemotherapy cycles, further progression of the disease was observed during chemotherapy. Computed tomography (CT) performed at that time showed generalized lymphadenopathy and the presence of an irregular area in left thyroid lobe. On palpation, the thyroid was asymmetrical, with enlarged left lobe and palpable lymph node packages on the left side of the neck. The levels of thyroid hormones and anti-thyroid antibodies were normal. Ultrasound examination of the thyroid gland showed non-homogeneous hypoechogenic structure of the left lobe and complete focal remodeling. Cytological examination of left-lobe lesion obtained during fine needle aspiration biopsy showed multiple small lymphoid cells, suggestive of small lymphocytic lymphoma. To confirm this diagnosis, flow cytometry of the biopsy material sampled from the left lobe was performed showing B cellimmunophenotype: CD19+/CD20+/CD22 dim/FMC-7, CD23+/CD5+, sCD79b-+, CD38-, CD10-, kappa and lambda-/weak reaction. The results of flow cytometry of the thyroid bioptate and blood were nearly identical, confirming leukemic nature of the infiltration in left thyroid lobe. Cytogenetic findings included the presence of 17p deletion (TP53 gene). The patient received immunochemotherapy with alemtuzumab. The progression of the disease occurred in the sixth week of therapy. The treatment was discontinued after 8 weeks due to worsening of patient's general status. The patient died 15 months after the diagnosis.

The use of recombinant human activated protein C (rhAPC) in the treatment of severe sepsis in immunosuppressed patients in the course of hematological diseases.

BACKGROUND: Treatment of hemopoietic system neoplasias involves severe complications associated with immunosuppression. We present two cases of treating severe sepsis utilizing recombinant human activated protein C (rhAPC) in the course of bilateral pneumonia in patients with hairy cell leukemia (HCL) and T-cell acute lymphoblastic leukemia (ALL). RhAPC, limited the coagulation cascade by inactivating FVa and FVIIIa, directly and indirectly limiting systemic inflammatory response syndrome (SIRS), and improved the fibrinolysis process. These actions break the pathomechanism of sepsis and improve survival. CASE REPORT: Besides intensive, multidirectional treatment of severe sepsis, Xigris (activated drotrecogin alfa) was administered on the second day in both cases. The infusion continued, as recommended, for 96 hours without complications. During treatment the patients' general condition and respiratory efficiency improved, allowing respirator weaning on days 5 and 8 of therapy. These cases of severe sepsis and immunosuppression indicate a high therapeutic efficacy of drotrecogin alfa (activated). Treatment outcome was uncertain because of the patients' hematological condition, so rapid restoration of respiratory efficiency and no disease progression after discontinuing treatment was a great success, possibly due to implementing Xigris at a relatively early stage of sepsis and the intensive therapy conducted according to Surviving Sepsis Campaign guidelines. CONCLUSIONS: Patient survival in severe sepsis directly depends on early diagnosis and institution of treatment. 1. These cases confirm the effectiveness of drotrecogin alfa in severe sepsis as part of multidirectional therapy. 2. Microorganisms causing atypical pneumonia should be considered in diagnosing infections in patients treated with cytostatic agents.