Tijekom pandemije virusa SARS-CoV-2 onkološki pacijenti označeni su kao posebno rizična skupina. Posebnu skupinu čine pacijenti u tijeku imunoterapije inhibitorima kontrolnih točaka. Čini se kako su ...koristi imunoterapije u bolesti koje uzrokuje novi koronavirus potpuno potisnule početni strah od očekivanih negativnih utjecaja imunosnog sustava potaknutog inhibitorima kontrolnih točaka. Sprječavanjem iscrpljenosti CD8+ limfocita, smanjenjem razine interleukina-6 i indirektnom regulacijom neutrofila i NK stanica, imunoterapija djeluje na patofiziologiju razvoja blažih oblika bolesti COVID-19. Trenutne spoznaje ističu imunoterapiju kao sigurnu opciju onkološkog liječenja u doba pandemije COVID-19.
With regard to systemic oncological treatments, correlation of the use of immunotherapy with checkpoint inhibitors with the risk of more severe COVID-19 infection is uncertain. However, benefits of immunotherapy in the disease caused by the new coronavirus completely suppressed the initial fear of expected negative impacts of immune system triggered by checkpoint inhibitors. By preventing CD8 + lymphocyte exhaustion, reducing interleukin-6 levels, and indirectly regulating neutrophils and NK cells, immunotherapy affects the pathophysiology of COVID-19. The current findings highlight immunotherapy as a safe option of cancer treatment at the time of COVID-19 pandemic.
Lichen planus is recognized as a T-cell-mediated disease. Histologically, it is characterized by the formation of colloid bodies representing apoptotic keratinocytes. The apoptotic process mediated ...by CD8(+) cytotoxic T lymphocytes (CTLs) and NK cells mainly involves two distinct pathways: the perforin/granzyme pathway and the Fas/FasL pathway. So far, little is known regarding the role of perforin-mediated apoptosis in lichen planus. In the present study, the expression and distribution of perforin, T and NK cell subsets in the epidermis and dermis of lesional and nonlesional lichen planus skin were studied. Skin biopsy specimens from lesional and nonlesional skin of ten patients with lichen planus and eight healthy persons were analysed by immunohistochemistry. Significant accumulation of T cells, particularly of CD4(+) and CD8(+) subsets, was found in both epidermis and dermis of lichen planus lesions compared with nonlesional and healthy skin. There were no significant differences in the incidence of NK cells (CD16(+) and CD56(+)) between lesional, nonlesional and healthy skin. Perforin expression was significantly upregulated in the epidermis of lichen planus lesions. In conclusion, accumulation of perforin(+) cells in the epidermis of lichen planus lesions suggest a potential role of perforin in the apoptosis of basal keratinocytes.
It is still controversial whether keratoacanthoma is to be considered as a well differentiated variant of squamous cell-carcinoma or a separate entity. As opposed to malignant potential of squamous ...cell-carcinoma, keratoacanthoma is characterized by a spontaneous regression. However, in some cases, otherwise typical keratoacanthoma can behave aggressively showing the signs of perineural and perivascular invasion and metastases in regional lymph nodes. The most important feature that separates these two closely related entities is a tendency of keratoacanthoma to regress. Causes and detailed mechanism of this regression are still not completely elucidated.
Within the past few years, it has become evident that the molecular events regulating cell survival and apoptosis are important contributors to the overall kinetics of benign and malignant cell growth. Immunological mechanisms have been implicated in a phenomenon of spontaneous tumor regression. Recent studies suggested that the tumor regression is dependent mainly on the immune response mediated by cytotoxic T lymphocytes (CD8+), together with helper T cells (CD4+). Cytotoxic T lymphocytes can kill tumor cells and mediate tumor regression in vivo through two distinct molecular mechanisms: Fas/Fas ligand and granzyme B/perforin mediated pathways.
Tumor cells are capable of developing different escape mechanisms in order to overcome their sensitivity to apoptotic signals. However, granzyme B, contained in cytolytic granules released upon target cell recognition, can also cause tumor cell death and consequently tumor regression by direct damage to non-nuclear structures through a caspase-independent pathway.
Therefore, we propose a key role of plasticity in the granzyme B mediated cell death pathway in the killing of changed tumor cells, resulting in keratoacanthoma regression through apoptosis or direct damage of tumor cells. On the other hand, insufficient activation of cytotoxic T lymphocytes and decreased release or activity of granzyme B could be responsible for squamous cell-carcinoma progression and occasional aggressive behavior in keratoacanthomas.
As a first step in confirming or refuting our hypothesis, we suggest a thorough immunohistochemical study of the presence of granzyme B and its activity in keratoacanthoma and squamous cell-carcinoma samples. To our knowledge, no such study has been performed so far.
The goal of this study was to identify risk factors for wound infections in patients with oral cancer who underwent surgical procedures.
This study included 195 patients who underwent surgical ...treatment of oral and oropharyngeal cancer over a 7-year period. Wound infection was defined as the occurrence of purulent content from the wound or as an appearance of exudate with signs of local infection and positive cultures taken from the wound. For every patient who was suspected to have a wound infection, a swab from the wound was taken, and microbiological analysis was performed. The patients were divided into 2 groups: patients with postoperative wound infections, and patients with postoperative wound infection.
Wound infection was present in 155 patients (59%). Univariate analysis indicated that the following factors were significantly related to the occurrence of wound infection: gender, smoking, tumor localization, size and stage of the tumor, type of surgery, neck dissection, type of reconstruction, nasogastric sonde, gastrostomy and tracheotomy. On multivariate analysis, statistically significant predictors of wound infection were gender, tumor localization and type of reconstruction.
The occurrence of wound infection is high despite antibiotic prophylaxis. To minimize the risk of wound infection and for prompt recognition of risk factors, surgeons managing oral tumor patients should have a better understanding of the risk factors such as gender, tumor localization and type of reconstruction.
Abstract
Introduction
Merkel cell carcinoma is a rare and aggressive primary cutaneous neuroendocrine malignant tumor. The tumor has a high rate of local recurrence after surgical removal. ...Spontaneous regression appears to be relatively common in this rare type of tumor.
Case presentation
We describe the clinical course, cytological and histological findings of a Merkel cell carcinoma in a 70-year-old Caucasian woman, simultaneously diagnosed with chronic lymphatic leukemia. The tumor showed clinical regression after fine needle aspiration. At primary presentation, the tumor had no apparent leukocyte infiltration, but was completely cleared by T-cell mediated immunity within 3 weeks after fine needle aspiration.
Conclusion
Fine needle aspiration may have acted as a mechanical trigger involved in the activation of cell-mediated immunity, leading to the clinical and histological regression of the tumor. To the best of our knowledge, this is the first case report of spontaneous regression of Merkel cell carcinoma in a patient with a co-malignancy, that is to say, chronic lymphocytic leukemia.
Malignant melanoma (MM) is known to avoid the host’s immune response. Studies on in vitro melanoma cell lines link the microphthalmia-associated transcription factor (MITF) with the regulation of the ...PD-L1 expression. It seems that MITF affects the activation of the gene responsible for PD-L1 protein expression. Several proteins, including Bcl-2 and Cyclin D1, play major roles in malignant melanoma cell cycle regulation and survival. Our study aims to assess the relationship between MITF, Bcl-2, and cyclin D1 protein expression and the expression of the PD-L1 molecule. Additionally, we examined the association of BRAF mutation, MITF, and CCND1 gene amplification with PD-L1 protein expression. We performed immunohistochemical staining on fifty-two tumour samples from patients diagnosed with nodular melanoma (NM). BRAF V600 mutation, MITF, and CCND1 gene amplification analyses were analyzed by the Sanger sequencing and QRT-PCR methods, respectively. Statistical analyses confirmed the significant inverse correlation between cyclin D1 and PD-L1 expression (p = 0.001) and correlation between PD-L1 and MITF protein expression (p = 0.023). We found a statistically significant inverse correlation between the present MITF gene amplification and PD-L1 (p = 0.007) and MITF protein expression (p = 3.4 ×10–6), respectively. Our study, performed on clinical NM materials, supports the in vitro study findings providing a rationale for the potential MITF-dependent regulation of PD-L1 expression in malignant melanoma.
Abstract Melanoma ulceration is the third most powerful survival predictor in the analysis for the currently valid 2010 AJCC melanoma staging system. However, there is still no detailed explanation ...for melanoma ulceration mechanism. Although thicker tumors are more commonly ulcerated, ulceration is a factor that predicts the disease outcome independently of melanoma thickness. It is our hypothesis that EGFR activates melanoma cell mobility. Melanoma cells with increased mobility move through tissue in diverse direction. Cells moving toward the epithelium weaken the intercellular bonds between the cells causing the loss of epithelium and subsequently ulceration.
Novel molecular techniques including markers of laryngeal carcinogenesis could improve the difficult diagnosis of a wide array of laryngeal polypoid changes. The case reported herein shows that not ...every clinically diagnosed vocal fold polyp is a benign lesion as mostly considered in the literature. Further assessment including carcinogenesis markers detected a nest of micro-invasive squamous cell carcinoma. Therefore, we recommend biopsy backed up with immunohistochemical analysis whenever there is a suspicious polypoid formation in order to exclude or confirm a malignant transformation because of the possibility of multi-focal growth in the active laryngeal epithelium.
Nove molekularne tehnike, uključujući markere laringealne karcinogeneze, mogu pridonijeti diferencijalnoj dijagnozi širokog spektra polipoidnih promjena grkljana. Prikazujemo slučaj koji ukazuje na to da nije svaka klinički dijagnosticirana polipoidna lezija glasnica benigna kao što se obično navodi u literaturi jer smo daljnjom imunohistokemijskom obradom otkrili žarište mikroinvazivnog planocelularnog karcinoma. Stoga kod svake polipoidne tvorbe grkljana preporučujemo biopsiju popraćenu imunohistokemijskom analizom markera kako bi se potvrdila ili isključila maligna transformacija zbog poznate sklonosti multifokalnom rastu u aktivnom epitelu grkljana.
Sažetak. Nove molekularne tehnike, uključujući markere laringealne karcinogeneze, mogu pridonijeti diferencijalnoj dijagnozi širokog spektra polipoidnih promjena grkljana. Prikazujemo slučaj koji ...ukazuje na to da nije svaka klinički dijagnosticirana polipoidna lezija glasnica benigna kao što se obično navodi u literaturi jer smo daljnjom imunohistokemijskom obradom otkrili žarište mikroinvazivnog planocelularnog karcinoma. Stoga kod svake polipoidne tvorbe grkljana preporučujemo biopsiju popraćenu imunohistokemijskom analizom markera kako bi se potvrdila ili isključila maligna transformacija zbog poznate sklonosti multifokalnom rastu u aktivnom epitelu grkljana.
U Hrvatskoj je zabilježen 2,7 postotni godišnji porast mortaliteta od melanoma kože. U više studija otkriveno je da osobe koje razviju melanom na abdomenu imaju znatno veći broj madeža od osoba koje ...razviju melanom na glavi ili vratu. Suprotno tome, melanomi na glavi i vratu povezani su sa solarnom keratozom, ali vrlo slabo s brojem madeža. Otkrivena je povezanost podtipa lentigo maligna melanoma sa značajnim izlaganjem suncu, ali nikakve konstantne korelacije nisu pronađene kod drugih histoloških podtipova. Nova molekularno genetska istraživanja snažno podržavaju koncept da su melanomi nastali na centralnim dijelovima tijela kod mlađih osoba s velikim brojem melanocitnih madeža biološki različiti od melanoma nastalih kumulativnim djelovanjem na suncem oštećenoj koži starijih ljudi i da su madeži i melanomi istog puta nastanka vođeni istim genetskim promjenama. Epidemiološke stručne analize brzo su utvrdile da visok stupanj izloženosti suncu znači veći broj madeža u ranom djetinjstvu. Višestruka istraživanja pokazala su da BRAF-mutirajući melanomi najčešće spadaju u superficijalno-šireći podtip i pojavljuju se na koži koja je povremeno bila izložena suncu kao i da češće metastasiziraju u regionalne limfne čvorove nego melanomi bez BRAF mutacija. KIT-mutiranimelanomi se pojavljuju u koži, na noktima, na mukozi ili na koži koja je oštećena suncem te najčešće isključuju BRAF mutaciju. Melanomi s ovom mutacijom vrlo često imaju in situ komponente koje su slabo ograničene, što je rezultat pojačane lateralne mobilnosti neoplastičnih melanocita nakon aktivacije SCF KIT puta.
PDF
