The relevance of macrocytosis induction during neoadjuvant dose-dense chemotherapy in breast cancer patients.

The aim of this study was to explore the red blood cell changes that occur during neoadjuvant dose-dense chemotherapy (NAC) of breast cancer. Also, we investigated the role of macrocytosis as a predictive biomarker for pathological complete response and disease-free survival (DFS) in these patients. A retrospective analysis of 82 breast cancer patients' data treated with anthracycline-cyclophosphamide-paclitaxel (AC-T) NAC in three oncology institutions in south Croatia from 2013 to 2020 was carried out. During chemotherapy mean corpuscular volume increased with time, with a median increase of 7.25 fl. Macrocytosis was induced in 38% of patients overall. Development of macrocytosis did not correlate with DFS [hazard ratio = 0.525; 95% confidence interval (CI), 0.074-3.768; P = 0.525]. Higher percentage of patients in macrocytosis group achieved PCR, 39% vs. 29% in no macrocytosis group, but this difference was not statistically significant. The relevance of macrocytosis induction during dose-dense neoadjuvant chemotherapy in breast cancer should be further explored.

COVID-19 Pandemic Effects on Breast Cancer Diagnosis in Croatia: A Population- and Registry-Based Study.

BACKGROUND: Our objective was to assess the effects of COVID-19 antiepidemic measures and subsequent changes in the function of the health care system on the number of newly diagnosed breast cancers in the Republic of Croatia. SUBJECTS, MATERIALS, AND METHODS: We performed a retrospective, population- and registry-based study during 2020. The comparator was the number of patients newly diagnosed with breast cancer during 2017, 2018, and 2019. The outcome was the change in number of newly diagnosed breast cancer cases. RESULTS: The average monthly percent change after the initial lockdown measures were introduced was -11.0% (95% confidence interval - 22.0% to 1.5%), resulting in a 24% reduction of the newly diagnosed breast cancer cases in Croatia during April, May, and June compared with the same period of 2019. However, during 2020, only 1% fewer new cases were detected than in 2019, or 6% fewer than what would be expected based on the linear trend during 2017-2019. CONCLUSION: It seems that national health care system measures for controlling the spread of COVID-19 had a detrimental effect on the number of newly diagnosed breast cancer cases in Croatia during the first lockdown. As it is not plausible to expect an epidemiological change to occur at the same time, this may result in later diagnosis, later initiation of treatment, and less favorable outcomes in the future. However, the effect weakened after the first lockdown and COVID-19 control measures were relaxed, and it has not reoccurred during the second COVID-19 wave. Although the COVID-19 lockdown affected the number of newly diagnosed breast cancers, the oncology health care system has shown resilience and compensated for these effects by the end of 2020. IMPLICATIONS FOR PRACTICE: It is possible to compensate for the adverse effects of COVID-19 pandemic control measures on breast cancer diagnosis relatively promptly, and it is of crucial importance to do it as soon as possible. Moreover, as shown by this study's results on the number of newly diagnosed breast cancer cases during the second wave of the pandemic, these adverse effects are preventable to a non-negligible extent.

Impact of HER2 receptor status on axillary nodal burden in patients with non-luminal A invasive ductal breast carcinoma.

BACKGROUND: Breast cancer (BC) is the most common malignancy in women. AIM: To assess the impact of HER2 status on axillary lymph node (ALN) involvement in patients with invasive ductal carcinoma of no special type (IDC-NST) both at diagnosis and during the 4-year postoperative period. PATIENTS AND METHODS: We retrospectively included 375 women with an early clinical stage of non-luminal IDC-NST who between 2007 and 2013 underwent breast surgery at a clinical hospital. They were divided into phenotype-based groups: HR+HER2-, HR+HER2+, HR-HER2+ and HR-HER2-. Only patients with sentinel lymph node (SLN) macrometastases underwent ALN dissection. If > 3 ALNs were positive, radiotherapy was delivered. All patients were treated with chemotherapy, HER2+ BC patients received trastuzumab, and hormone receptor (HR)-positive BC patients received hormonal therapy. RESULTS: Larger tumor size, higher grade, HR+, HER2+ status, and lymphovascular invasion (LVI) were predictive for ALN metastases at diagnosis. The poorest overall, disease-free, and distant recurrence-free survival (OS, DFS, DRFS) were found in the HR-HER2- group, while the poorest locoregional recurrence-free survival (LRFS) was observed in HR-HER2+ and HR-HER2- groups. HER2 status was not predictor of survival. CONCLUSIONS: HER2+ status was predictive for ALN involvement at diagnosis but had no effect on 4-year LRFS in these patients.

[Analysis of sentinel lymph node in early breast cancer patient - Clinical Hospital Center Rijeka]. / Analiza limfnog cvora cuvara u bolesnica s ranim invazivnim rakom dojke - Klinicki bolnicki centar Rijeka.

Sentinel lymph node (SLN) biopsy is an accurate method for the detection of axillary metastases in early breast cancer patients and is of value as a replacement for axillary dissection. However, variations in the methods and protocols used for the pathological evaluation of SLN exist in everyday practice. Therefore, standardization how to detect, dissect, process, stain, assess and report SNL is required in order to stratify patients into adequate prognostic groups. The aim of this study was to present our experience in SLN analysis in patients with early breast cancer and clinical stage T1-2 and N0. In the period between 2003 and 2011, 1071 consecutive patients or 1915 SLN were analyzed. The protocol included intraoperative analysis of histological frozen sections and cytological imprint, followed by analysis of paraffin sections according to the protocol that included sections of whole SLN with the interval of 250 prm. According to the accepted protocol 75% of SLN were negative. The obtained results were correlated with literature data.

The Challenges and Opportunities of the Implementation of Comprehensive Genomic Profiling in Everyday Clinical Practice with Non-Small Cell Lung Cancer: National Results from Croatia.

Non-small cell lung cancer (NSCLC) has become the best example of precision oncology's impact on outcomes in everyday clinical practice, significantly changing the expectations of all stakeholders, including medical professionals, society, and most importantly, patients. Consequently, the implementation of the precision oncology concept in medical systems, in order to achieve optimal and proven curative effects in NSCLC, is imperative. In this study, we investigated the development, challenges, and results associated with the implementation of precision oncology in NSCLC on a national level in Croatia. We conducted a multicenter, retrospective, cross-sectional analysis on the total population of Croatian patients with metastatic lung cancer, on whose tumors specimen comprehensive genomic profiling (CGP) testing was performed during 2020 and 2021. A total of 48 patients were included in the study. CGP revealed clinically relevant genomic alterations (CRGA) in 37 patients (79%), with a median of 2 (IQR 1-3) CRGA per patient. From the panel of recommended tests, KRAS, MET, and EGFR were the most common alterations, detected in 16 (34%), 5 (11%), and 3 (6%) patients, respectively. CGP revealed additional targetable mutations in 29 (60%) patients who would not have been tested (and consequently, whose mutations would not have been detected) according to the existing everyday standard of practice in Croatia. The tumor mutational burden was reported as high (≥10 Muts/Mb) in 19 patients (40%). CGP analysis reported some kind of targeted therapy for 34 patients (72%). CGP revealed other potentially targetable mutations, and it also determined TMB to be high in a significant number of patients. In conclusion, when possible, CGP should be used as an upfront backbone diagnostic and treatment-oriented work-up in patients with NSCLC.

HSP70 In triple negative breast cancer: Prognostic value and clinical significance.

BACKGROUND: Triple-negative breast cancer (TNBC) has the worst prognosis and the highest immunogenic potential of all breast cancer subtypes. It is characterized by a lack of estrogen and progesterone receptors as well as HER2. A major component of the tumor microenvironment (TME) of TNBC is tumor-infiltrating lymphocytes (TILs). A chaperone heat shock protein 70 (HSP70) is involved in several pathways that enable tumour growth and progression, as well as in immune modulation. METHODS: Immunohistochemical analysis of HSP70 expression in immune cells, as well as expression of immunosuppressive markers CTLA4 and PD-L1 and major TILs components: CD8, CD4 and Tregs were analyzed in the superficial and deep tumor layer of primary TNBC and compared with established clinicopathological parameters. Clinical data and surgical tissue samples from 68 TNBC patients who underwent initial surgery were included in the analysis and 36 control samples from benign breast tissue biopsies. RESULTS: A higher expression of TILs, CD4, CD8 and PD-L1 was found in the invasive tumor front (ITF), as compared to the tumor center (TC) (p < 0001). HSP70 positive immune cells (HSP70(+) IC) in TC were associated with adverse clinical and pathological markers: higher stage of disease (P = 0.013), higher grade (P = 0.05) and a higher pN status (P < 0.001). In addition, higher expression of HSP70(+) IC from TC was correlated with the higher expression of FOXP3(+)T cells both in ITF (N = 61, rho=0.42, p < 0.001) and in metastatic tissue from the draining lymph nodes (N = 13, rho=0.61, P = 0.026). CONCLUSION: Correlations between HSP70 immune cells expression and individual TILs components support the hypothesis of its active role in inducing immunosuppression and tumor progression. Routine determination of HSP70 expression, in immune cells of TC, may be of added value in the clinical decision-making process concerning axillary surgery.

Comprehensive Genomic Profiling in the Management of Ovarian Cancer-National Results from Croatia.

Today, in the era of precision medicine, the determination of genomic instability or other potentially targetable mutations, along with BRCA 1 and BRCA 2, is a crucial component of the diagnosis and treatment management of advanced ovarian cancer. Advanced technologies such as next-generation sequencing (NGS) have enabled comprehensive genomic profiling (CGP) analysis to become more feasible for routine use in daily clinical work. Here, we present the results for the first two years of an analysis of patients with advanced ovarian cancer on a national level. The aim was to establish the position of CGP in the daily clinical practice of treating ovarian cancer. We performed a multicenter, retrospective, cross-sectional analysis on the total population of Croatian patients who were newly diagnosed with locally advanced or metastatic ovarian cancer or whose initial disease had progressed from 1 January 2020 to 1 December 2021, and whose tumors underwent CGP analysis. All 86 patients (100%) analyzed with CGP had at least one genomic alteration (GA). The median LOH was 14.6 (IQR 6.8-21.7), with 35 patients (41%) having an LOH ≥ 16. We found BRCA-positive status in 22 patients (26%). Conventional testing, which detects only BRCA mutations, would have opted for therapy with PARP inhibitors in 22 (26%) of our patients. However, CGP revealed the need for PARP inhibitors in 35 patients (41%). The results identified a significantly higher number of women who would achieve a possible benefit from targeted therapy. Hence, we believe that CGP should be a backbone diagnostic tool in the management of ovarian cancer.

The "round block" surgical technique in the management of multicentric fibroadenomas.

The "round block" surgical technique in the treatment of a female patient with multiple, multicentric fibroadenomas in both breasts is presented. The advantages of this technique for patients with multicentric benign breast lesions are minimal postoperative scar and a favourable aesthetic result. Breast dimensions and the areolar diameter were measured in 203 subjects of Primorsko-Goranska county during examination in the Out-Patient Hospital for Breast Diseases, including the operated patient. Smaller breast dimensions and a larger areolar diameter provide an easier access to any part of the breast due to a smaller distance between the incision and a fibroadenoma and a larger circumference of circular periareolar incision, thus facilitating the surgery. The analysis of average, maximum and minimum values measured shows that the "round block" technique can be performed in all cases of multiple and multicentric fibroadenomas regardless of breast size, areolar diameter and the location of fibroadenoma in the breast.

Evaluation of adjuvant chemotherapy in patients with colorectal cancer in Primorsko-Goranska and Istarska County--a twenty years retrospective study.

Colorectal cancer is the second most common malignant disease in developed countries, with about one million new cases worldwide every year, accompanied with high mortality rate. We examined the survival rate and recurrence (occurrence of distant metastases and/or local recurrence) of patients with colorectal cancer in Primorsko-Goranska and Istarska County who received adjuvant chemotherapy, compared to those who did not in the period since 1980. until 1999. This study involves 483 patients with colorectal cancer stages II and III of Primorsko-Goranska and Istarska County, which were underwent curative resections of colorectal cancer at the Clinical Hospital Centre Rijeka, and then treated with chemotherapy (288) or without Chemotherapy (195). We analyzed the five year survival rate and the recurrence of malignant disease in the adjuvant treatment group in comparison with not treated group with chemotherapy, depending on the stage of disease, degree of histological differentiation, patient age and location of cancer (colon or rectum). After follow-up of 60 months died 44.79% (129/288) of patients who received chemotherapy and 53.33% (104/195) of patients who did not receive chemotherapy. The relative risk of death (from any cause) in chemotherapy-treated group versus the group without chemotherapy was 0.82 (p < 0.008). Recurrence of malignant disease in the chemotherapy group was 38.54% (111/288), and in the group without chemotherapy was 46.15% (90/195). The relative risk of recurrence of malignant disease in the chemotherapy group versus the group without chemotherapy was 0.78 (p < 0.001). There was no difference in treatment efficacy regard to the localization of the tumor, but there were differences in efficiency with respect to disease stage, grade and age. Chemotherapy with 5-fluorouracil and leukovorin ameliorate the survival and reduces recurrence and distant metastases in patients with colorectal cancer stages II and III.

[Clinical recommendations for diagnosing, treatment and monitoring patients with non-small cell lung cancer]. / Klinicke upute za dijagnozu, lijecenje i pracenje bolesnika oboljelih od karcinoma pluca nemalih stanica.

In Croatia, lung cancer is the most common malignant disease among male population and the third common among female population where 85% of patients have non-small cell lung cancer. Due to significance of this disease it is necessary to define and implement standardized approach for diagnostic and treatment algorithm as well to patients monitoring. Several multidisciplinary sessions were organized in achieving this goal. The sessions' results are given in the form of the Clinical guidelines.

Is it too expensive to fight cancer? Analysis of incremental costs and benefits of the Croatian National Plan Against Cancer.

This cost-effectiveness study analyses the expected impacts of activities proposed by the Croatian National Plan Against Cancer (NPAC) on cancer incidence and survival rates, as related to their respective costs. We evaluated the impact of the NPAC on two main outcomes, namely, reduced incidence and the improved survival of cancer patients, expressed as life years gained (LYGs), which enabled the calculation of incremental cost-effectiveness ratios (ICERs) in the form of cost per LYG. In the analysis of costs, we considered both the direct costs of NPAC activities as well as the wider indirect societal costs of cancer, thus permitting the calculation of the ICER both from the narrower national health insurer's perspective (accounting only for the direct costs) and the wider societal perspective (accounting both for the direct and indirect costs). We estimated that on average, for all patients benefiting from the implementation of the NPAC in Croatia, an additional LYG would be yielded at the additional cost of €1.021 (societal perspective). The NPAC can, for some sites, even be considered a dominant intervention due to the negative cost/LYG ratio, meaning that it generates additional LYGs while at the same time, reducing total societal costs. Taking a narrower health insurer's perspective (i.e., accounting only for the direct costs), the NPAC produces an additional LYG at an additional cost of €1.408. Both cost per LYG estimates can be considered cost-effective investment options.

Spiritual Well-Being for Croatian Cancer Patients: Validation and Applicability of the Croatian Version of the EORTC QLQ-SWB32.

Spiritual well-being is a recognized predictor of health-related quality of life in palliative patients. No research in Croatia has yet addressed this field. This study, the first of its kind in Croatia, validated a Croatian translation of the EORTC QLQ-SWB32 measure of spiritual well-being with curative Croatian oncology patients and assessed its use and value. The study was conducted between July 2019 and January 2020 at the Department of Radiotherapy and Oncology, University Hospital Rijeka, with 143 cancer patients, using the linguistically validated Croatian version of the measure. All patients found the measure acceptable. Confirmatory factor analysis aligned with the structure found in previous studies. Cronbach's alpha confirmed internal consistency. Female participants scored higher on the RSG (Relationship with Someone or Something Greater), RG (Relationship with God), and EX (Existential) scales, and on Global-SWB. Patients with breast and gynecological tumors scored higher on RG. Older patients scored lower on RSG, RG and EX. Retirees and those with below-average incomes scored lower on EX. Participants who identified as having no religion scored lower on RSG. Stage I cancer patients scored higher on RG. The Croatian version of the EORTC QLQ-SWB32 is an acceptable, valid, and reliable measure of SWB for Croatian cancer patients.

Precision Oncology in Metastatic Uterine Cancer; Croatian First-Year Experience of the Comprehensive Genomic Profiling in Everyday Clinical Practice.

Comprehensive genomic profiling (CGP) is gradually becoming an inevitable part of the everyday oncology clinical practice. The interpretation and optimal implementation of the results is one of the hot topics of modern-day oncology. According to the recent findings, uterine cancer harbors a high level of gene alterations but is still insufficiently explored. The primary goal of this project was to assess the proportion of patients with targetable mutations. Also, the aim was to define and emphasize potential opportunities as well as the problems we have faced in the first year of testing on the national level. We performed a multicentric, retrospective, nested cross-sectional analysis on the total population of Croatian patients with advanced/metastatic uterine cancer where the tumor CGP was performed during 2020. CGP of the tumor tissue of 32 patients revealed clinically relevant genomic alterations (CRGA) in 27 patients (84%) with a median of 3 (IQR 1-4) CRGA per patient. The most common CRGAs were those of phosphatide-inositol-3 kinases (PIK3) in 22 patients (69%), with 13/22 (59%) of those patients harboring PIK3CA mutation. The next most common CGRAs were ARID1A and PTEN mutations in 13 (41%) and 11 (34%) patients, respectively. Microsatellite status was determined as stable in 21 patients (66%) and highly unstable in 10 patients (31%). A high tumor mutational burden (≥10Muts/Mb) was reported in 12 patients (38%). CGP analysis reported some kind of targeted therapy for 28 patients (88%). CGP determined clinically relevant genomic alterations in the significant majority of patients with metastatic uterine cancer, defining it as a rich ground for further positioning and development of precision oncology.

Real-World Efficacy and Safety of Bevacizumab in the First-Line Treatment of Metastatic Cervical Cancer: A Cohort Study in the Total Population of Croatian Patients.

BACKGROUND: Although today it is almost preventable, cervical cancer still represents a significant cancer burden, especially in some developing parts of the world. Since the introduction of bevacizumab in the first-line treatment of metastatic disease, improvements of the outcomes were noted. However, results from randomized controlled trials are often hard to recreate in the real-world setting. OBJECTIVE: To assess the real-world efficacy and safety of bevacizumab as a first-line treatment of advanced cervical cancer. METHODS: We conducted a retrospective cohort study on the total population of Croatian patients diagnosed with metastatic cervical cancer from 2016 to 2019 who were treated with bevacizumab in combination with cisplatin and paclitaxel (TCB) in the first line. The comparison group was the consecutive sample of patients treated with chemotherapy alone. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response rate, incidence of adverse events, and the proportion of treatment discontinuation. RESULTS: We enrolled 67 patients treated with TCB and a control group of 62 patients treated with chemotherapy alone. The TCB cohort had significantly longer unadjusted OS with a median of 27.0 (95% CI 18.5; not calculable) months, compared to 15.5 (10.7; 30.1) months in the chemotherapy-alone cohort. Adjusted OS was not significantly different. PFS was significantly longer for the TCB cohort, with a median of 10.6 (95% CI 8.5; 15.4) months, than for the chemotherapy-alone cohort, with a median of 5.4 (95% CI 3.9; 9.1) months, even after adjustment for baseline covariates (HRadjusted = 0.60; 95% CI 0.39; 0.94; p=0.027; false discovery rate <5%). CONCLUSIONS: In a real-world setting, TCB as a first-line treatment of metastatic cervical cancer was associated with longer PFS, better objective disease control rate, and acceptable toxicity profile in comparison to chemotherapy alone. These results may indicate its utility and potential applicability in other parts of the developing world.

Lung cancer and environmental chemical exposure: a review of our current state of knowledge with reference to the role of hormones and hormone receptors as an increased risk factor for developing lung cancer in man.

Lung cancer is a dominant cause of cancer mortality. The etiology of lung cancer is mainly related to cigarette smoking, airborne genotoxic carcinogens, and arsenic, but its sex-specific incidence suggests that other mechanisms, such as hormones, may also be involved in the process of carcinogenesis. A number of agents commonly present in the living environment can have dual biological effects: not only are they genotoxic / carcinogenic, but they are also hormonally active as xenoestrogens. This dualism may explain sex-specific differences reported in both types and incidence of lung cancer. In a novel approach to investigate the complexity of lung cancer, etiology, including systems biology, will be used as a tool for a simultaneous interpretation of measurable environmental and biological parameters. Using this approach, the etiology of human lung cancer can be more thoroughly investigated using the available data from oncology and environmental health. The information gained could be applied in the introduction of preventive measures, in personalized medicine, and in more relevant legislation, which should be adjusted to reflect the current knowledge on the complex environmental interactions underlying this life-threatening disease.

Olaparib Outcomes in Patients with BRCA 1-2 Mutated, Platinum-Sensitive, Recurrent Ovarian Cancer in Croatia: A Retrospective Noninterventional Study.

Our objective was to assess the safety and efficacy of olaparib in maintenance therapy of BRCA 1-2 mutated, platinum-sensitive, recurrent ovarian carcinoma after the partial or complete response to the second or further lines platinum-based chemotherapy in a real-world setting. We performed a multicenter, real-world observational population-based cohort study on the whole population of Croatian patients initiated to olaparib maintenance therapy between 2016 and 2020. The primary endpoints were progression-free survival and the discontinuation of treatment because of adverse events. We enrolled the total population of 69 patients with the median (interquartile range; IQR) age of 53 (48-59), 56 (81%) of them with BRCA1 mutation. The median (IQR) follow-up was 16 (9-25) months. Treatment had to be discontinued because of toxicity in 2 (3%) and temporarily interrupted in 14 (20%), while dose was reduced because of toxicity in 18 (26%) of patients. Toxicity of any grade was observed in 61 (88%) patients and toxicity of grade 3 or 4 in 12 (17%). Median progression-free survival was 21 (95% CI 16-not calculable) months from the introduction of olaparib, and the median overall survival was not reached. Our study confirmed efficacy and safety of olaparib as the maintenance therapy of BRCA 1-2 mutated, platinum-sensitive, recurrent ovarian carcinoma. We observed the real-world efficacy and safety comparable to those observed in the randomized controlled trials. We found the interesting observation of better efficacy of 300 mg tablets, compared to 400 mg capsules, an issue that should be addressed on much larger real-world populations.

Prognostic value of IMP3 immunohistochemical expression in triple negative breast cancer.

Triple negative breast cancer (TNBC) account for 12% to 17% of all breast cancers. It is a heterogeneous group of tumors associated with aggressive clinical course. Insulin-like growth factor II mRNA binding protein 3 (IMP3) belongs to a family of insulin-like growth factor type II (IGF2), which plays a key role in the transmission and stabilization of mRNA, cell growth, and migration during embryogenesis. Increased expression of IMP3 is associated with aggressive behavior of different tumor types, advanced clinical stage, distant metastasis, and shorter overall survival (OS).The study included 118 patients with breast carcinoma diagnosed as TNBC and immunohistochemical staining for estrogen receptors (ER), progesterone receptors (PR), epidermal growth factor receptor 2 (HER2/neu), Ki-67, and IMP3 was performed. Correlations between categorical variables were studied using the chi-square and the Mann-Whitney U test. For survival analysis, the Kaplan-Meier method, log-rank test and the Cox proportional hazard regression model were used.Positive expression of IMP3 protein was present in 35.6% of TNBC. The presence of basal morphology was observed in 46.6% of TNBC. Positive IMP3 expression was connected with larger size of tumor, higher clinical stage, and basal morphology (P = .039, P = .034, P < .001). Disease-free survival and OS were significantly shorter in IMP3 positive TNBC.According to results of our study IMP3 expression can be used as negative prognostic factor for triple negative breast carcinomas. Targeting IMP3 molecule could be an effective approach to the management of a triple negative breast cancer with new immunological therapies, which does not yet exist for this group of tumors.

Recurrent amelanotic melanoma of nasal cavity: Biological variability and unpredictable behavior of mucosal melanoma. A case report.

The aim of this report is to present a case of a patient with a recurrent nasal cavity amelanotic melanoma (AM), with emphasis on diagnosis and therapy options of this clinical entity. A 65-year-old female patient presented with pain in the right cheek region and nasal obstruction. In 2013, she was diagnosed with mucosal melanoma (MM) of the left nasal cavity. After endoscopic surgery and radiotherapy, the patient was followed by the oncology team. Five years after the initial diagnosis, rhinoscopy showed a tumorous formation in the right nasal cavity. The tumor mass was without black discoloration and was the same color as the surrounding nasal mucosa. Microscopic examination after biopsy of the tumor confirmed amelanotic MM. The patient underwent an additional endoscopic surgery. A complete standard diagnostic workup for MM found metastases in head and neck lymph nodes, on both sides. MMs of head and neck are uncommon malignancies. Unique biology of MM cells causes a high rate of recurrences. This report presents an example of recurrent AM of the nasal cavity, in treatment with checkpoint inhibitor (pembrolizumab), which could provide a good therapy option for patients with MM.

Merkel cell carcinoma arising in the ear canal.

A case of rare tumor, Merkel cell carcinoma, located in the ear canal of a 25-year-old woman is presented. A polypoid tumor mass was extirpated, and tympanoplasty was done at the first operation, whereas at the second operation, all the bones of the ear canal were removed. Epitympanum and cavum were filled with tumor, and the tumor mass was removed in toto. The histopathology and immunohistochemical staining characteristics of tumor confirmed the presence of Merkel cell tumor. Postoperatively, radiation therapy to the tumor bed was completed. There was no clinical or radiographic evidence of recurrence or metastasis of Merkel cell tumor for 3 years.

Kaposi's sarcoma in an HIV-negative chronic lymphocytic leukemia patient without immunosuppressive therapy: A case report.

Kaposi's sarcoma is a neoplasm of endothelial cells. That vascular tumor is usually limited to the skin, but it may involve mucous membranes, visceral organs, and lymph nodes. Serological evidence has shown that human herpesvirus 8 infection is required for the development of Kaposi's sarcoma. Chronic lymphocytic leukemia is the most common leukemia all over the world. Increased skin cancer risk has been reported for patients with chronic lymphocytic leukemia. The relation between these two pathologies has not yet been clarified. We report a case of Kaposi's sarcoma along with chronic lymphocytic leukemia in a patient who did not receive therapy for chronic lymphocytic leukemia.