Morphologic-Molecular Transformation of Oncogene Addicted Non-Small Cell Lung Cancer.

Patients with non-small cell lung cancer, especially adenocarcinomas, harbour at least one oncogenic driver mutation that can potentially be a target for therapy. Treatments of these oncogene-addicted tumours, such as the use of tyrosine kinase inhibitors (TKIs) of mutated epidermal growth factor receptor, have dramatically improved the outcome of patients. However, some patients may acquire resistance to treatment early on after starting a targeted therapy. Transformations to other histotypes-small cell lung carcinoma, large cell neuroendocrine carcinoma, squamous cell carcinoma, and sarcomatoid carcinoma-have been increasingly recognised as important mechanisms of resistance and are increasingly becoming a topic of interest for all specialists involved in the diagnosis, management, and care of these patients. This article, after examining the most used TKI agents and their main biological activities, discusses histological and molecular transformations with an up-to-date review of all previous cases published in the field. Liquid biopsy and future research directions are also briefly discussed to offer the reader a complete and up-to-date overview of the topic.

Investigation of Autologous Fat Transfer in Capsule Formation around Silicone Implants in a Rat Model.

BACKGROUND: In this experimental study, the authors investigated whether fat placement in the pocket during implant insertion affects capsule formation. METHODS: Twenty albino Wistar rats, 400 g each, were used. The rats were divided into two groups, A and B, of 10 rats each. At the dorsum of each rat, four pockets (2 × 2 cm each) were dissected, two left and two right of the midline. In each pocket, a 1 × 1 × 1.5-cm silicone implant was inserted. In the two left pockets, only silicone implants were placed (control). In the two right pockets, 0.4 ml of fat was injected around the implant. Animals in group A were killed 2 months postoperatively, and those in group B were killed 4 months postoperatively. The implants were dissected with the capsule and sent for histopathologic examination. RESULTS: The data of the fat transfer group was compared with control in groups A and B. Capsule thickness, neovascularization, myofibroblast layer thickness, and mast cell population demonstrated no statistically significant difference in either group A (p = 0.385, p = 0.862, p = 0.874, and p = 0.210, respectively) or group B (p = 0.338, p = 1.000, p = 0.288, and p = 0.344, respectively). Inflammation was statistically significantly less (p = 0.07) at 4 months (group B) in the fat transfer group compared to the control group. Likewise, cellularity was statistically significantly less (p = 0.019) at 4 months for the fat transfer group compared with the control group. CONCLUSION: Fat injection in the pocket during implant placement may reduce inflammation and cellularity of capsules and predispose to faster capsule maturation. CLINICAL RELEVANCE STATEMENT: Fat transfer around implants may positively affect implant-based breast reconstruction and/or breast augmentation.

Nonsurgical treatment of capsular contracture: Review of clinical studies.

Capsular contracture is one of the most distressing complications of breast implant use in both aesthetic and reconstructive plastic surgery procedures. This systematic review was performed to assess the effectiveness of all nonsurgical treatments for established capsular contracture.

Primary melanoma of the cornea.

Purpose: To present an extremely rare case of corneal melanoma. Method: An 84-year-old female patient presented to our department with a pigmented corneal lesion in her right eye (OD), 6x4 mm, complaining of mild pain and inability of complete eyelid closure. Tumor growth had been noted the previous year. She had undergone cataract surgery in her right eye three years before, followed by an unspecified postoperative complication. Her visual acuity was 3/10 OD and 9/10 OS. Ophthalmic evaluation and ultrasonography (A- and B-scan) did not reveal any other pathology. The pigmented lesion was surgically removed and the patient underwent a protocol therapy of topical chemotherapy (mitomycin 0.03%, 2x4 for 2 weeks and dexamethasone 0.1%, 2x4 for the following 2 weeks, followed by another cycle of mitomycin 0.03%, 2x4 for another 2 weeks). Results: The surgical removal of the lesion was uncomplicated, as was the postoperative period. The patient's visual acuity improved to 6/10 three months postoperatively. The histologic examination revealed malignant melanoma. Conclusions: Despite its rarity, primary melanoma of the cornea is an existing entity. Treatment of corneal melanoma consists of surgical removal and postoperative topical chemotherapy. Postoperative follow-up is mandatory.

TdT expression in normal and neoplastic sebaceous cells.

AIMS: Terminal deoxynucleotidyl transferase (TdT) is a DNA polymerase expressed in immature, normal and neoplastic, lymphoid or haematopoietic cells and in neuroendocrine carcinomas, such as Merkel cell carcinoma and small-cell carcinoma. It has not yet been described in cells of epithelial origin. After observing TdT immunoreactivity in normal sebaceous glands, we analysed its spectrum of expression in cases of sebaceous cell hyperplasia (SGH) and sebaceous cell neoplasm. METHODS AND RESULTS: Twelve cases of SGH and three cases of other benign lesions, namely sebaceoma, sebaceous adenoma, and sebaceous naevus, along with four archived cases of sebaceous cell carcinoma (SC) were collected and stained with TdT antibody. In addition, tissue microarrays were constructed from 11 cases of basal cell carcinoma (BCC) and 10 cases of squamous cell carcinoma (SCC), which had nine evaluable cases each, and, after carcinoma type confirmation with immunostaining for epithelial membrane antigen, TdT immunohistochemistry was performed. All cases of SGH and sebaceous cell neoplasm were positive for TdT. The staining intensity was variable, being often weak to moderate in a significant proportion of cells, apart from one case of SC and the case of sebaceous naevus, which were only focally positive. No BCCs and only one SCC showed immunoreactivity. CONCLUSIONS: TdT protein can be found in cells of epithelial origin and specifically sebaceous cells, both benign and malignant. It can be hypothesized that this expression is due to sebaceous cell differentiation as a prelude to apoptosis and holocrine secretion. Additional studies are needed to further elucidate its biological role.