Case Report: Epithelioid angiosarcoma of the pleura.

Introduction: We present the case of a patient with recurrent bilateral hemothorax. After misdiagnosis despite several histological samples, a pleural manifestation of epithelioid angiosarcoma was diagnosed by further immunohistological staining. Based on this situation, we aim to sensitize the reader to this rare disease. Main concerns and important clinical findings: A 73-year-old fully conscious woman presented with dyspnea for 3 days. She was in stable general condition, pain was denied, she had a history of cigarette smoking, she had no cardiopulmonary events, and she was not receiving any anticoagulation medication. Physical examination revealed decreased breath sounds on the left side, and her hemoglobin level was 7.0 mmol/L. Primary diagnoses interventions and outcomes: The initial chest x-ray showed a left-sided effusion. Hemothorax was then diagnosed. Further investigation revealed no evidence of malignancy (CT, EBUS, cytology, etc.). VATS was performed, and biopsies of pleural lesions did not reveal congruent findings for the hemothorax. Due to recurrent bilateral hemothorax with the need for erythrocyte transfusion, the patient underwent several operations, including histological sampling, without evidence of malignancy. After further processing, an additional pathological report revealed an epithelioid angiosarcoma defined by massively proliferating epithelioid cells strongly positive for ERG and CD31 and negative for CD34. The neoplastic cells coexpressed D2-40 (podoplanin). Finally, due to multiple cerebral metastases, palliative therapy was indicated. Conclusion: Physicians and pathologists treating spontaneous hemothorax need to have broad knowledge of the possible, sometimes rare, etiologies. If the clinical course and intraoperative findings do not agree with the histopathological results, this finding must be questioned, and further immunohistochemical staining is mandatory. Thus, in the case of recurrent hemothorax, angiosarcoma of the pleura should also be considered for differential diagnosis.

Laparoscopic surgery for colorectal cancer in an elderly population with high comorbidity: a single centre experience.

PURPOSE: The use of laparoscopic surgery for colorectal cancer in elderly patients with high comorbidity is a controversial subject. This retrospective analysis aims to compare two different age groups with respect to short and long term clinical and oncological outcomes. METHODS: All laparoscopic colorectal resections for cancer performed between February 2011 and October 2017 with curative or palliative intention were evaluated. RESULTS: Among 128 completed resections, the rate of major complications, length of hospital stays, 30-day mortality, 2-year recurrence rate, and the survival after palliative surgery were comparable between group A (< 75 years; n = 76) and B (≥ 75 years; n = 52). Patients in group B showed an extraordinarily high proportion of ASA III stage (73.1% vs. A: 35.5%; p < 0.01) and, in this context, an increased rate of minor postoperative complications (17.3% vs. A: 6.6%; p < 0.05) and lower overall 2 and 5-year survival rates. Within the first 2 years, they died sooner in the event of recurrence (57.1% vs. A: 18.2%; p < 0.05), and their survival after rectal resection, especially for low rectal carcinoma, was significantly reduced (58.8% vs. A: 96.7%; p < 0.001). CONCLUSION: Laparoscopic surgery for colorectal cancer can be strongly advocated for elderly patients even in the face of high comorbidity. Whether very old patients with low rectal carcinoma also benefit from minimally invasive surgery or should undergo alternative therapies would need to be clarified primarily by examining the quality of life.

Metabolic Disorders/Obesity Is a Primary Risk Factor in Hidradenitis Suppurativa: An Immunohistochemical Real-World Approach.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory, potentially scarring disease of the hair follicle, affecting the apocrine gland-bearing skin areas. The major comorbid disorders associated with the occurrence or the aggravation of the disease are obesity and smoking. Numerous efforts to dissociate these factors led to controversial results. OBJECTIVES: To assess the importance of metabolic disorders/obesity, smoking/environmental toxins, and inflammation in HS by utilizing the differential expression of major relevant protein markers in lesional skin of obese/smoking versus non-obese/non-smoking HS patients. METHODS: Lesional skin specimens deriving from two groups of HS patients (BMI >30 and smokers, n = 12 vs. BMI <30 and non-smokers, n = 10) were stained with antibodies raised against irisin, PPARγ, and IGF-1R, which correlate with metabolic disorders/obesity, EGFR and AhR, associated with smoking, and IL-17, IL-17R, and S100A8, as markers of inflammation. RESULTS: Metabolic disorders/obesity-related markers exhibited marked differential expression between the two groups, while smoking-associated markers a limited one. IL-17R expression was stronger in obese/smokers, and S100A8 staining exhibited intense strong immunoreactivity in both groups without significant difference. CONCLUSIONS: The notion that obesity plays a role in HS development appears to be supported by the prominent regulation of the associated lesional biomarkers. Tobacco smoking might contribute less to HS than previously suspected.

Increased Activity and Number of Epidermal Melanocytes in Lesional Psoriatic Skin.

BACKGROUND: Psoriatic lesions may resolve with hypo- or hyperpigmentation. The involvement of melanocytes in this dichotomous clinical outcome is not fully investigated. OBJECTIVES: Qualitative and quantitative assessment of melanocytes in untreated lesional and non-lesional psoriatic skin (n = 15) and healthy controls (n = 10). METHODS: Skin biopsies were labelled immunohistochemically (APAAP technique) with the antimelanocyte monoclonal antibodies (MoAbs) HMB45, Melan A, tyrosinase and microphthalmia-associated transcription factor (MITF). The labelled melanocytes were evaluated by an independent investigator with a digital image analyser. RESULTS: Lesional melanocytes, in contrast to those in non-lesional and healthy skin, exhibited features of activation in the form of dilatation, prominent and long dendrites and intense labelling. The number of melanocytes was significantly increased in psoriatic lesions in comparison with non-lesional psoriatic and healthy skin as shown by counts of cells labelled with the MoAbs HMB45 (3-fold; p < 0.001), Melan A (1.6-fold; p < 0.01) and tyrosinase (1.5-fold; p < 0.01). In contrast, labelling with MITF revealed no significant difference (1.2-fold increase; p > 0.05). Likewise, no significant difference between non-lesional psoriatic and healthy skin control was found (p > 0.05). Furthermore, no positively labelled dermal cells were detected, apart from few only detected with Melan A. CONCLUSIONS: Epidermal melanocyte activity and numbers are increased in the epidermal compartment of psoriatic lesions providing an explanation for postinflammatory hyperpigmentation.

Ex vivo human skin and SZ95 sebocytes exhibit a homoeostatic interaction in a novel coculture contact model.

The sebaceous gland displays key functions of the human skin, such as hormone synthesis in situ, antimicrobial activity and participation to inflammatory responses. Consequently, there is an emerging need of advanced in vitro models to study complex interactions between the sebaceous gland and the other skin compartments. Despite the evolution of both full-skin organ culture and reconstructed three-dimensional skin models, no satisfactory solutions have been provided for the integration of sebaceous glands and/or sebaceous gland cells in those models, probably due to their problematic maintenance both in vitro and ex vivo. We have developed a coculture model of explant skin in direct contact with immortalized SZ95 sebocytes, which resulted in overall improved structural integrity of the epidermis, higher percentage of proliferating basal epidermal cells and reduced apoptosis of differentiating keratinocytes after 6 days, as detected by Ki67 and TUNEL staining, respectively. Furthermore SZ95 sebocytes exhibited morphological and biochemical signs of normal differentiation and lipid accumulation, while interleukin-6 expression in the supernatant of the cocultures was decreased in comparison with the control. The data provide evidence of a beneficial interaction between sebocytes and skin explants and provide the rationale for their integration in future three-dimensional skin models.

Juvenile-like (inflammatory/hyperplastic) mucosal polyps of the gastrointestinal tract in neurofibromatosis type 1.

AIMS: Diffuse neurofibromatosis/ganglioneuromatosis, solitary/plexiform neurofibroma, periampullary carcinoids and gastrointestinal stromal tumour (GIST) are the main gastrointestinal manifestations of neurofibromatosis type 1 (NF-1, von Recklinghausen disease). Inflammatory (juvenile-like) polyps have not been recognised to date as specific gastrointestinal (GI) manifestations of NF-1. METHODS AND RESULTS: We describe four males aged 23-65 years with NF-1 and inflammatory (juvenile-like) gastrointestinal polyps, and review the literature for similar cases. Two patients had single polyps (sigmoid colon and antrum, respectively), one had two polyps (left colon), and one had three polyps (distal oesophagus and colon). Histological appearances were variable, ranging from juvenile-like to granulation tissue-rich, predominantly inflammatory and hyperplastic. Three lesions showed obliterative vasculopathic changes. None had neurofibromatous or ganglioneuromatous polyps. A review of the literature disclosed 11 similar cases. Most patients presented with severe gastrointestinal symptoms and/or anaemia. CONCLUSIONS: NF-1-associated inflammatory polyps probably represent specific GI manifestations of this disorder, and should be considered, particularly in patients with GI symptoms. They should be distinguished from inflammatory fibroid polyps and from juvenile-like changes associated with ganglioneuroma/ganglioneuromatosis and neurofibroma/neurofibromatosis. Their aetiology remains obscure, but different mechanisms, including NF-1 inactivation, NF-1-associated vasculopathy, and localised mucosal prolapse/damage caused by motility disorders, might be involved.

Spectrum of KIT/PDGFRA/BRAF mutations and Phosphatidylinositol-3-Kinase pathway gene alterations in gastrointestinal stromal tumors (GIST).

Pathogenetic pathways of gastrointestinal stromal tumors (GIST) lacking mutations in KIT and PDGFRA (∼15%) are still poorly studied. Nearly nothing is known about PI3K alterations in GISTs and only a few GISTs with BRAF mutations have been reported. BRAF mutations (V600E) were found in 3/87 tumors (3.5%) concomitantly were wild type for KIT and PDGFRA. No mutations were detected in KRAS, NRAS, and FGFR3. For the first-time we demonstrated a PIK3CA mutation (H1047L) simultaneously occurring with a 15-bp deletion in KIT exon 11 in one tumor. We suggest that BRAF mutations are of pathogenetic significance in wild type GISTs. The PI3K pathway should be assessed in future studies.