Metastatic Skin Lesions Research Articles

Aberrant activation of AXL may drive progression of squamous cell carcinoma in CLL patients: a mechanistic study with clinical implications.

Occurrence of squamous cell carcinoma (SCC) even in early-stage, untreated chronic lymphocytic leukemia (CLL) patients can be a significant morbidity issue with occasional transformation into metastatic skin lesions. CLL cells and extracellular vesicles (EVs) from CLL patients' blood/plasma were purified and used. Expression/activation of AXL and its functions in normal keratinocytes (HEKa) were assessed in vitro co-culture system and in SCC tissues. We detected aberrant activation of AXL, AKT and ERK-1/2 in SCC cell lines compared to HEKa. We also detected increased expression of AXL in primary SCC tissues obtained from CLL patients. Increased activation of AXL, AKT, ERK-1/2 and Src was discernible in HEKa upon co-culturing with CLL cells. Further analysis suggests that Gas6, a ligand of AXL, regulates AXL activation in co-cultured HEKa. Interestingly, exposure of HEKa cells to CLL plasma-derived EVs induced expression of AXL, P-AKT, and EMT-associated markers leading to migration of the cells. Finally, pharmacologic inhibition of AXL induced cell death in SCC lines in a dose dependent manner. Our findings that CLL cells likely are involved in driving SCC progression, at least in part, via activation of the AXL signaling axis, indicating that AXL inhibition may be beneficial for our CLL patients with SCC.

Skin Involvement

Abstract Skin involvement can occur at the beginning of a septic episode (primary skin and soft tissue infections) or during its progression (secondary or metastatic skin lesions), making skin a useful accessible tissue in the study of septic patients. The objective of this study was to determine the overall prevalence of sepsis-related skin findings and evaluate their possible prognostic value. A retrospective, single-center study of septic patients with documented bloodstream infections admitted in a tertiary hospital in 2019 was carried out. Unselected samples of 320 episodes of sepsis from 265 patients were included. Skin lesions were documented in 83 septic episodes from 69 patients (25.9%). Skin involvement was more frequently associated with bloodstream infections caused by Staphylococcus aureus (P = 0.0001), coagulase-negative staphylococci (P = 0.036), and Pseudomonas aeruginosa (P = 0.005). Mean hospital stay (37.58 vs 27.82 days, P = 0.023) and sepsis-related mortality (18.1% vs 11.0%, P = 0.024) were higher in patients with skin lesions than in individuals without them. Our results suggest that skin involvement (primary and/or secondary) is an unfavorable indicator in the evolution of septic patients with bloodstream infections. Thorough examination of the skin is recommended in the routine evaluation of septic patients, whether or not the origin of the infection is known.

Clinical and morphological features of eccrine acrospiroma: analysis of literature data and case from practice.

Eccrine acrospiroma is a rare benign tumor of the skin arising from the epithelial cells of eccrine sweat ducts. The clinical picture is characterized by its variability, so a detailed morphological study of the operative material is necessary to establish a diagnosis. Differential diagnosis must be carried out with hemangioma, melanoma, infected sebaceous cyst, metastatic skin lesion, and other tumors from elements of the sweat gland. In the article the authors presented the clinical and morphological analysis of own case from practice of large eccrine acrospiroma on the back surface of the left thigh which was diagnosed in a 56-year-old man.

Invasive fusariosis.

Invasive fusariosis is a serious invasive fungal disease, affecting immunocompetent and, more frequently, immunocompromised patients. Localized disease is the typical clinical form in immunocompetent patients. Immunocompromised hosts at elevated risk of developing invasive fusariosis are patients with acute leukemia receiving chemotherapeutic regimens for remission induction, and those undergoing allogeneic hematopoietic cell transplant. In this setting, the infection is usually disseminated with positive blood cultures, multiple painful metastatic skin lesions, and lung involvement. Currently available antifungal agents have poor in vitro activity against Fusarium species, but a clear-cut correlation between in vitro activity and clinical effectiveness does not exist. The outcome of invasive fusariosis is largely dependent on the resolution of immunosuppression, especially neutrophil recovery in neutropenic patients.

Invasive Fusariosis in Patients with Hematologic Diseases.

Fusarium species are filamentous fungi widely encountered in nature, and may cause invasive disease in patients with hematologic conditions. Patients at higher risk are those with acute leukemia receiving induction remission chemotherapy or allogeneic hematopoietic cell transplant recipients. In these hosts, invasive fusariosis presents typically with disseminated disease, fever, metastatic skin lesions, pneumonia, and positive blood cultures. The prognosis is poor and the outcome is largely dependent on the immune status of the host, with virtually a 100% death rate in persistently neutropenic patients, despite monotherapy or combination antifungal therapy. In this paper, we will review the epidemiology, clinical manifestations, diagnosis, and management of invasive fusariosis affecting patients with hematologic diseases.

The role of electrochemotherapy with intratumoral bleomycin for early tongue carcinoma

Background The role of electrochemotherapy (ECT) using intratumoral bleomycin and electroporation as a first line treatment for oral tongue carcinoma has not been defined. Aims/Objectives To evaluate the method of ECT in oral tongue carcinoma. Material and Methods Twenty-one successive patients with primary T1-T2 oral cancer predominantly of the oral tongue underwent either ECT (test; n = 9), or standard surgical resection and reconstruction (control; n = 12). Outcome variables were: local recurrence rates, 10-year-survival, adverse events, treatment cost, and quality of life. Results The 10-year local recurrence rate (44.4%) was higher and the tumour-specific survival rate (55.6%) was lower in the ECT group compared to the control group (17% and 91.6%, respectively). Postoperative haemorrhage, dysphagia, and pain were more frequent in ECT patients, treatment time was shorter, but treatment cost was higher. Quality of life was not improved by ECT. Conclusions and Significance Our results indicate that ECT seems not as suitable for the treatment of early tongue cancer as it is for neoplastic and metastatic skin lesions and less favourable than standard surgical therapy.

Utility of Fine-Needle Aspiration Cytology in Diagnosis of Cutaneous and Subcutaneous Metastasis

Introduction: Cutaneous metastasis (CM) is an uncommon clinical presentation and poses trouble in diagnosis. However, it is remarkable and can occur due to a known or an unknown primary tumor. Despite the fact that clinical assessment helps in the diagnosis, Fine-needle aspiration cytology (FNAC) is a modest, basic, and quick principle line of investigation for the finding of CM. Materials and Methods: It was a retrospective study conducted in the department of pathology at a tertiary care teaching hospital. The study was conducted from January 2010 to May 2020. All cases of CM that has been diagnosed by FNAC were included. Results: During the study period, a total of 37 cases of CM were observed, constituting 0.15% of all FNACs. The age of the patients ranged from 35 to 74 years, and the male: female ratio was 1.05:1. Primary tumor was known in all 37 cases. Among males, lung carcinoma was the more common whereas breast was the most common organ of primary among females. The most common lesion was a single nodule (27 cases), with predominant site being chest wall (32.5%), and the most common tumor at microscopy was metastatic adenocarcinoma. Conclusion: FNAC is a fast and safe procedure that can be utilized as a first line of investigation in diagnosing metastatic skin lesions. Basic assessment of cytomorphology alongside significant clinical subtleties could help in recognizing the site of an unknown primary.

Frequency and Spectrum of Cutaneous Metastases of Visceral Malignancies: A Retrospective Observational Study of Three Years Duration in a Tertiary Care Hospital.

Background:In spite of the skin being the largest organ of the body, cutaneous malignancies are uncommon especially in people of color as compared to the white population. The incidence of cutaneous metastases of visceral malignancies is further low and accounts for 0.5% to 10% of cancer cases as per written literature. Cutaneous metastasis as the presenting sign of underlying internal malignancy is extremely rare and is a marker of poor prognosis. Limited data is available in written literature about the frequency and spectrum of metastatic skin lesions in the Asian population.Objective:1) To find the frequency of metastasis of visceral malignancies in skin biopsies. 2) To evaluate the clinicopathological presentation and immunohistochemistry (IHC) profile of cutaneous metastases.Subjects and Methods:It is a retrospective analysis of all the skin biopsies received in our department of Pathology for HPE from 01 Jan 2017 till 31 Dec 2019. Cases of cutaneous malignancy were segregated into primary and metastatic categories. Clinical details of the cases of cutaneous metastases were retrieved and analyzed. All the cases of cutaneous metastases were studied in detail for their clinical presentation, histomorphological features, and findings on IHC.Results:Out of a total of 484 skin biopsies in 3 years, 9.7% showed features of malignancy. Total ten cases of cutaneous metastases (2%) were found, out of which three were the primary presentation of silent visceral malignancy. The lung, breast, colon, and ovary were the common primary sites to manifest as cutaneous metastases with the abdominal wall being the commonest site. Histomorphological features aided by the IHC panel helped in diagnosing the cutaneous metastases and site of the primary malignancy.Conclusion:Cutaneous metastasis as the primary presentation of visceral malignancy is rare and should not be missed as it indicates a poor prognosis. Clinico-pathological correlation and histomorphological features assisted by IHC markers help pathologists in diagnosing the site of primary malignancy in cases of cutaneous metastases.

Differential expression of androgen receptor variants in hormone-sensitive prostate cancer xenografts, castration-resistant sublines, and patient specimens according to the treatment sequence.

Androgen receptor variants (AR-vs), especially AR-v7 and AR-v 5, 6, and 7 exon-skipped (AR-v567es), are reportedly key players in the development of castration-resistant prostate cancer (CRPC). We previously established a mouse xenograft model (JDCaP) from a metastatic skin lesion from a Japanese patient with CRPC and that was revealed to exhibit androgen sensitivity. In the present study, we established multiple castration-resistant xenograft models from JDCaP mice to investigate the biological features of CRPC. Tissue from JDCaP mice was transplanted into male and female nude mice, and after serial passaging, castration-resistant sublines (JDCaP-CR2M and JDCaP-CR4M in male mice, JDCaP-CR2F and JDCaP-CR4F in female mice) were established. We investigated anti-androgen and testosterone sensitivity and the messenger RNA expression pattern of full-length AR and AR-vs. In addition, we compared AR protein levels of patient specimens among primary, local-recurrent, and two skin-metastatic tumors. All JDCaP-CR sublines showed continuous growth following the administration of bicalutamide, although the effects of testosterone varied among sublines. Parental JDCaP and JDCaP-CR2M, JDCaP-CR4M, and JDCaP-CR4F sublines expressed AR-v7, whereas JDCaP-CR2F exhibited elevated AR-v567es expression resulting from genomic deletion, which was confirmed by DNA sequencing. Moreover, we confirmed AR-v7 expression in the tumor of the original patient after androgen-deprivation therapy. Each JDCaP-CR subline showed different AR-v-expression patterns, with JDCaP-CR2F expressing AR-v567es due to genomic deletion. Our results indicated that AR-vs emerged after androgen-deprivation therapy and appeared essential for acquisition of castration resistance.

Invasive mould disease in haematologic patients: comparison between fusariosis and aspergillosis

ObjectivesTo compare the epidemiology, clinical presentation, diagnosis, treatment, and outcome of haematologic patients with invasive aspergillosis (IA) or invasive fusariosis (IF). MethodsWe retrospectively reviewed the charts of 36 patients with IA and 26 with IF diagnosed between 2006 and 2017 in haematologic patients, and compared baseline characteristics, coexisting exposures, clinical manifestations, treatment, and the outcome. ResultsFever was more frequent in IF (96.2% vs. 63.9%, p 0.003), whereas pneumonia (88.9% vs. 50.0%, p 0.001) and sinusitis (63.9% vs. 38.5%, p 0.048) were more frequent in IA. Skin lesions and positive blood cultures occurred exclusively in patients with IF. Among patients with pneumonia, the halo sign was more frequent in IA (62.5% vs. 23.1%, p 0.02). Serum galactomannan was positive in 88.6% of patients with IA and in 73.3% with IF (p 0.18), with no differences in the median number of positive tests and galactomannan values. Positive serum galactomannan plus lung infiltrates was the predominant clinical presentation in IA and occurred in four of 13 patients with IF and lung involvement. The 30-day survival was 77.7% in IA and 46.1% in IF (p 0.01). ConclusionsIA and IF share the same epidemiologic scenario but different clinical presentations in the majority of cases, with disease in the airways in IA, and fever, metastatic skin lesions, and positive blood cultures in IF. However, a substantial proportion of patients with IF present with a clinical picture similar to IA, with fever, lung infiltrates, and positive serum galactomannan.

Pattern of skin cancer in north western region of Yemen

The pattern of skin cancer differs in different countries. The aim of this study is to identify the pattern of skin cancer in northwestern region in Yemen and to compare it to similar studies done in southern Yemeni governorates and in neighborhood. This is a descriptive prospective study of patients data with histologically diagnosed skin cancers carried out in the Saudi hospital in Sa'adah and Hajjah governorates in Yemen between Jan.2007 and Dec.2014. The data were collected and recorded on proforma and was analyzed according to the type of tumor, age and gender of the patients and anatomical site involved. Two histopathologists investigated the specimens. There were 324 Yemeni patients with skin malignancy, 204 were males (63%) and 120 were females (37%), the M: F ratio was 1.7:1. Most of the patients were over the age of 60 years and the mean age of all cases was 66.4 years. Squamous cell carcinoma was the most frequent (50%), followed by basal cell carcinoma (29%), Non-Hodgkin's lymphoma (4.9%), malignant melanoma (4%), and Kaposi's sarcoma (3.7%). Other rare primary skin cancers such as basosquamous carcinoma, adnexal carcinoma, dermatofibrosarcoma protuberans, neuroendocrine carcinoma, extramammary Paget's disease and aggressive angiomyxoma were recorded. Metastatic skin lesions were seen in six patients. The patterns of skin cancer in northwestern governorates of Yemen are nearly similar to international studies with higher incidence of squamous cell carcinoma. Head and neck was the most common affected site, followed by lower extremities. Community education about the risk of long exposure to sunlight is important, including coverage of the head and neck when working outdoor under sunny weather.

An update on cutaneous melanoma in Turkey: evaluation of 19-year data in a single tertiary centre and review of the literature.

Information on frequency of melanoma and its clinicopathological subtypes derived from dermatology clinics in Turkey is limited. As data about melanoma show clear differences due to geographic and ethnic distribution, we scrutinized the rich data of our dermatology centre in Istanbul. Consecutive patients diagnosed with melanoma in a tertiary dermatology clinic during the last 19 years were retrospectively investigated about the clinical presentation of the skin lesions during admission, frequency of subtypes and localization of the tumour. There were 227 patients with melanoma showing five different clinical presentations: 200 of them had totally 207 primary cutaneous melanoma (PCM) lesions, nine had PCM lesions associated with metastatic skin lesions, three presented with local recurrence, eight with only skin metastases and seven with regressed skin melanoma following systemic melanoma metastases. Histologically, 23.19% of the PCM lesions were intraepidermal (in situ) and Breslow thickness was less than 1 mm in 30.9% of the patients with invasive melanoma. The most common subtype was superficial spreading melanoma (SSM) (37.19%), followed by lentigo malignant melanoma (LMM) (31.4%), acral lentiginous melanoma (ALM) (19.32%) and nodular melanoma (NM) (6.76%). Head and neck region was the most common (34.78%) localization of PCM lesions. Different clinical presentations, including various types of cutaneous melanoma metastases, were seen. However, a great proportion of our patients were relatively early diagnosed, either having an in situ or an invasive PCM with a Breslow thickness ≤1 mm. Even though SSM was the most common subtype of PCM in our series, its rate was lower compared to many European countries. Furthermore, the rate of NM subtype was also low, while LMM and ALM rates were higher in comparison to studies originating from European countries. This striking discrepancy requires further studies to explain the probable causes.

Abstract P4-13-04: Upregulation of cell cycle pathway genes without loss of RB1 contributes to acquired resistance to single-agent treatment with palbociclib in breast cancer

Abstract Background: The oral cdk4/6 inhibitor, Palbociclib (Palbo), has been shown to prolong progression-free survival when combined with anti-estrogen therapy and have single-agent activity in metastatic breast cancer (MBC). Progressive disease (PD) on therapy does occur, however, and little is known about resistance mechanisms. Preclinical data have suggested that cell cycle gene expression changes are a potential mechanism of resistance. We performed comprehensive genomic analyses on serial tumor samples from an exceptional responder to single-agent Palbo to determine whether such changes occur in vivo. Methods: Serial biopsies were obtained from a 67 year old patient with MBC treated on a phase II trial of single-agent Palbo at the University of Pennsylvania. Tissue was obtained from the primary lesion (1999, Stage 3, ER-/PR+/Her2+) and first recurrence (2005, contralateral breast, bone, lung; ER+/PR-/Her2+, treated with Herceptin/letrozole). At PD (2010), pt received single-agent P, 50 mg daily for 21 days each 28-day cycle, with PR for 33 months. A sample from metastatic skin lesion at PD on P (2013) was obtained. Next generation targeted sequencing was performed at Foundation Medicine using the Heme Panel. RNA was profiled using a 784-gene custom Nanostring array including cell cycle genes and ER pathway genes. Determination of pathway enrichment was performed using GSEA and the statistical significance of network neighborhood over-representation was calculated using cumulative hypergeometric distribution. Results: There was no genetic evidence suggesting loss of RB1, or alterations in p16, cyclin D1, cdk4, PIK3CA or ESR1, and the genomic profile did not change between the primary and recurrent tissue samples. As expected, amplification of ERRB2 was present in all samples. In contrast, expression of cell cycle-regulated genes (PLK1, TOP2A, CDK1, BUB1, CDC20, CCNA2, CCNE2, CCNB1 BIRC5) increased more than two-fold at PD on Palbo compared to pre-Palbo, along with evidence of activation of the FOXM1 network. Conclusion: Gene expression changes associated with cell cycle activation and FOXM1 activation may lead to acquired resistance to Palbociclib, despite wild-type RB1. These data demonstrate the importance of pre-/post-treatment biopsies and the feasibility of high-level genomic assessment in archival tissues to elucidate resistance mechanisms of novel therapies. Citation Format: DeMichele A, Shih NNC, Koehler M, Huang Bartlett C, Jiang Y, Harwick J, Huang D, Zheng X, Clark AS, Colameco C, Feldman MD, Gallagher M, Goodman N, O'Dwyer P, Rejto P. Upregulation of cell cycle pathway genes without loss of RB1 contributes to acquired resistance to single-agent treatment with palbociclib in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-04.

Cutaneous Metastatic Rectal Adenocarcinoma in Zosteriform Distribution.

Dear Editor: A 54-year-old woman presented with mildly stinging, painful, grouped nodules on the left vulvar area. It shows unilateral localized grouped papulonodular lesions, resembling a zosteriform aspect (Fig. 1). The patient had a history of stage IV rectal adenocarcinoma with liver and lung metastases treated 17 months earlier with ultra-low anterior resection and chemotherapy. The patient also received external pelvic irradiation of 180 cGy/day, up to total 6,300 cGy/35 fractions, for recurrent adenocarcinoma at the anastomosis site. She presented with a zosteriform eruption on the left vulvar area during hospitalization, with no prior history of herpes zoster. The skin lesions exhibited predominantly nodular infiltration, inadequate for the tzanck test. A skin punch biopsy was performed under the differential diagnosis of herpes zoster on the left S2 dermatome, postherpetic granuloma, and cutaneous metastasis. Histopathology revealed metastatic adenocarcinoma (Fig. 2). The chest computed tomography (CT), abdomen CT, and positron emission tomographic-CT images showed consistent results of an increasing size of lung and hepatic nodules with lymph node metastasis. Pain around the vulva area was aggravated after repetitive chemotherapy and radiotherapy. Wide excision was performed to resect the visible cutaneous nodules with patient consent. The patient died eight months after the diagnosis of cutaneous metastasis, which was three years after the initial diagnosis of rectal adenocarcinoma. While the mean survival time from the diagnosis of cutaneous metastasis of colorectal cancer is 18 months1, our patient died in a shorter time span. Cutaneous metastasis from an internal malignancy is rare and can appear in many different forms, including the multiple nodular type, inflammatory or erysipeloid form, sclerodermoid form, alopecia neoplastica, or bullous form. The nodular type is the most common clinical appearance, while the zosteriform pattern is very rare2. The exact mechanism of zosteriform cutaneous metastasis is unknown. A Koebner-like phenomenon at the site of herpes zoster, invasion of the perineural lymphatic or dorsal root ganglion, direct invasion of tumor cells, and accidental surgical implantation have all been proposed 2,3. Colonofiberscopy and magnetic resonance imaging revealed an ulcerated fungating mass located on the left posterolateral wall of rectum. The metastatic lesion of the vulva was observed about 17 months later after a laparoscopic resection. However, an asymptomatic skin lesion may have appeared earlier. It is possible that the metastatic skin lesions may have been due to direct seeding of the tumor cells to the left side, but the exact mechanism remains unclear. The patient was undergoing chemotherapy when the metastatic lesions were observed, and herpes zoster occurs more frequently in immunosuppressed patients. It has been reported that many patients with cutaneous metastasis of zosteriform distribution are initially misdiagnosed with herpes zoster and treated with antiviral drugs4. Considering the pain and unilaterality, this may be easily misdiagnosed as herpes zoster. Herein, we report an unusual case of cutaneous metastasis of rectal adenocarcinoma that mimicked herpes zoster. This must be considered in any patient with a history of malignant neoplasm experiencing non-healing zosteriform lesions. Therefore, early biopsy for suspicious skin lesions is very important. Fig. 1 Stinging painful erythematous grouped nodules on the left vulvar area. Fig. 2 Dermal infiltration by intestinal type atypical glands, showing metastatic skin adenocarcinoma (H&E, ×100).

Distant skin metastases as primary presentation of gastric cancer.

Distant gastric metastasis to the skin is uncommonly a presenting symptom, although nonspecific paraneoplastic syndromes with dermatologic manifestation including diffuse seborrheic keratoses (Leser-Trelat sign), tripe palms, and acanthosis nigricans have been described in the literature. We report here the case of a 49-year-old woman with gastric adenocarcinoma who presented with cutaneous metastasis as an initial symptom. In our case, metastatic skin lesions responded significantly to EOX chemotherapy (epirubicin+oxaliplatin+capecitabine) despite progression of systemic disease. In similar presentations, a high index of clinical suspicion and skin biopsy are important.

Primary renal angiosarcoma with progressive clinical course despite surgical and adjuvant treatment: A case report

Angiosarcoma is an extremely rare, high-grade malignancy, which accounts for <2% of all soft-tissue sarcomas. Cases of primary renal angiosarcoma represent 1% of these. Angiosarcomas involving the kidney usually originate from metastatic skin lesions or primary visceral lesions and most often occur in the sixth and seventh decades of life. The present study describes a case of primary renal angiosarcoma that presented as a large right-sided renal mass with symptoms of flank pain. Despite surgical removal of the tumor, recurrent disease with associated lung metastases was identified at the surgical site following adjuvant chemotherapy. The patient succumbed to the disease 13 months after the diagnosis.

In Vitro and In Vivo Experiments on Electrochemotherapy for Bladder Cancer

Electrochemotherapy is widely performed to treat solid tumors but experience with bladder cancer is limited. We investigated mitomycin C and cisplatin administered with electrochemotherapy for bladder cancer in vitro and in vivo. The human bladder cancer cell line SW780 was used. Cells were treated with electroporation, drug alone or electroporation plus increasing concentrations of drug (mitomycin C 0.001 to 2,000 μM or cisplatin 1.56 to 300 μM). Electrochemotherapy parameters were 8 pulses of 1.2 kV/cm for 99 microseconds at 1 Hz. We investigated survival and apoptosis, the latter evaluated by caspase activity. NMRI-Fox1nu nude mice were inoculated subcutaneously and randomized to 1) electrochemotherapy plus NaCl, 2) NaCl alone, 3) electrochemotherapy plus drug or 4) drug alone (mitomycin C 5 mM or cisplatin 250 μM). Tumors were measured 3 times per week. A similar experiment was done to assess necrosis by histology at days 2 and 6. In vitro mitomycin C cytotoxicity and caspase activity was unaffected by electrochemotherapy (p = 0.9057 and 0.53, respectively). However, electrochemotherapy with cisplatin caused 6.6-fold increased cytotoxicity and higher caspase activity (p <0.0001 and <0.001, respectively). In vivo electrochemotherapy plus mitomycin C resulted in tumor volume reduction (p <0.0005). The survival rate in mice that received electrochemotherapy plus mitomycin C and mitomycin C alone was greater than in controls (p = 0.0004). The tumor response rate was 100% for electrochemotherapy plus mitomycin C, 53% for mitomycin C alone, 14% for electrochemotherapy plus NaCl and 0% for NaCl alone. In vivo electrochemotherapy plus cisplatin was associated with slower tumor growth over other combinations as well as significantly higher survival (p = 0.0005 and 0.0003, respectively). The tumor response rate was 47% for electrochemotherapy plus cisplatin, 0% for cisplatin alone, 0% for electrochemotherapy plus NaCl and 8% for NaCl alone In vivo electrochemotherapy with mitomycin C or cisplatin was more effective than chemotherapy alone in a bladder cancer tumor model, opening new perspectives in bladder cancer therapy.

Large Cell Neuroendocrine Carcinoma of the Ovary and Its Skin Metastases: A Case Report and Review of the Literature.

Large cell neuroendocrine carcinoma in the gynaecological organs affects the uterine cervix and ovary. Large cell neuroendocrine carcinoma of the ovary is extremely rare, and prognosis is quite poor even when diagnosed at an early stage. These tumours respond poorly to standard chemotherapy regimens. The clinical observation of skin metastasis in patients with epithelial ovarian cancer is relatively uncommon, occurring in only 3.5% of patients. These lesions are observed mostly in skin of the abdominal wall adjacent to the primary ovarian tumours. Metastatic skin lesions on extremities are much more rare; it is reported that only 12% of epithelial ovarian carcinoma skin metastases occur on the limbs. Skin metastasis due to large cell neuroendocrine carcinoma of the ovary has not been previously reported. We report the case of a large cell neuroendocrine tumour of the ovary with skin metastases on extremities appearing two months after surgery in a 68-year old woman.

Metastatic laryngeal carcinoma mimicking eruptive keratoacanthomas: report of keratoacanthoma-like cutaneous metastases in a radiation port

Metastatic skin lesions from a primary squamous cell carcinoma of the head and neck have only been reported in 1%-2% of these patients. Hence, skin metastases from laryngeal carcinoma are uncommon. Also, cutaneous metastases clinically presenting as a keratoacanthoma are rare. We describe cutaneous metastases in a radiation port clinically mimicking eruptive keratoacanthomas. Using the PubMed database, an extensive literature search was performed using the keywords cancer, carcinoma, keratoacanthoma, laryngeal, metastases, metastasis, metastatic, mimicking, port, radiation, radiotherapy, radiation, skin, visceral. We were able to summarize the features of patients with keratoacanthoma-like cutaneous metastases and discuss radiation port cutaneous metastases. Cutaneous metastases can be the initial manifestation of a previously undiagnosed malignancy or can present in a patient with an established diagnosis of cancer. Our patient not only developed skin metastases that mimicked eruptive keratoacanthomas, but to the best of our knowledge, is the first individual to develop radiation port cutaneous metastasis from a primary laryngeal carcinoma. The development of cutaneous metastases in an area of skin that has been treated with radiation therapy may result from the treatment altering and/or injuring the site, thereby making it more susceptible to another condition, such as metastatic skin tumors. In patients with an established diagnosis of visceral malignancy, the appearance of new keratoacanthoma-like lesions should prompt the clinician to consider a biopsy in order to establish or exclude the possibility of a cutaneous metastasis.

Multiple cutaneous metastases in laryngeal carcinoma: A rare occurrence

Metastasis to the skin in laryngeal squamous cell carcinoma is an extremely rare occurrence. We report a case of multiple cutaneous metastases in the follow-up of a 60-year-old male with squamous carcinoma of the vocal cords that were treated with surgery and radiotherapy. The patient presented with multiple painful skin nodules at 3 months following the completion of treatment. Clinically the skin nodules mimicked an inflammatory skin lesion. The diagnosis of metastatic skin lesions was made by cytological examination. Appearance of new painful skin lesions soon after the completion of treatment in patients treated for squamous carcinoma of the larynx should warrant a clinical suspicion of cutaneous metastases.