Immunocompromised cutaneous district, isotopic, and isopathic phenomena-Systematic review.

BACKGROUND: Although the development of lesions in skin areas that have undergone injury has long been known, understanding of its pathogenesis is limited. Depending on their peculiarities, those events have been described as isomorphic, reverse isomorphic, pseudoisomorphic, isotopic, and isopathic phenomena. Ruocco's immunocompromised cutaneous district (ICD) concept was proposed to include all those phenomena. AIMS: We performed a systematic review and critically evaluated the current understanding about ICD and its relationship with the isotopic and isopathic phenomena. METHODS: To illustrate the complexity of the theme, we present a case of subclinical leprosy, whose manifestation was brisk in an old tattoo. The possible interaction between the approached phenomena, acting in the genesis of the disease, made this a pertinent study. The research was conducted under the PRISMA-P guidelines, in seven biomedical databases between 1996 and 2018. The eligibility criteria were systematic reviews, meta-analyses, clinical studies, and case series, written in English, French, Italian, Portuguese, or Spanish. RESULTS: Using standardized keywords, 1220 articles were identified. After applying the eligibility criteria, 53 studies were selected. CONCLUSION: This review ratifies that all these phenomena are aspects of one single condition. They can be integrated into the ICD concept with the pathogenesis including: (a) neural damage (peripheral or central) and (b) chronic lymphedema. Both may change the local neuroimmune interaction. The identification of these phenomena and the understanding of their pathogenesis are of paramount importance, to define the diagnosis and choose the therapeutic strategy.

Prognostic significance of cyclooxygenase 2 and phosphorylated Akt1 overexpression in primary nonmetastatic and metastatic cutaneous melanomas.

Cyclooxygenase 2 (COX-2) and phosphorylated Akt1 (p-Akt1) are associated with tumor spreading, cell proliferation, high metabolism, and angiogenesis in solid tumors. This study aimed to investigate COX-2 and p-Akt1 expression in primary and metastatic melanomas by correlating with the cellular proliferation index (as revealed by minichromosome maintenance 2 expression) and the outcome of patients with malignant melanomas. Seventy-seven biopsies of malignant melanomas, including 42 primary nonmetastatic melanomas (PNMMs), 12 primary metastatic melanomas (PMMs), and 23 metastatic melanomas (MMs), were retrospectively selected. Tissue microarrays were developed and submitted for immunohistochemical staining for COX-2, p-Akt1, and minichromosome maintenance 2. Increased COX-2 cytoplasmic staining patterns were observed in PMM and MM when compared with PNMM (P=0.0011). Higher nuclear and cytoplasmic expression of p-Akt1 was more closely associated with PMM than with MM and PNMM (P<0.00001). Coexpression of these biomarkers was closely correlated with lower overall survival rates in melanomas. Furthermore, we observed a statistically significant positive correlation between the mitosis index and increased COX-2 expression (P=0.0135) and between p-Akt1 (P=0.0038) and the cellular proliferation index (P=0.0060). Taken together, our findings demonstrate that COX-2 and p-Akt1 play an important combined role during melanoma progression and are associated with highly metastatic tumors and survival rates in patients with MM. In addition, these biomarkers can be used to predict melanoma prognosis independently of metastatic status. However, further studies are required to elucidate the biological role of these biomarkers during the progression of MM events.

Granuloma Faciale and Eosinophilic Angiocentric Fibrosis: Similar Entities in Different Anatomic Sites.

BACKGROUND: Eosinophilic angiocentric fibrosis (EAF) and granuloma faciale (GF) share several histopathologic features, including eosinophil-rich inflammation, microangiitis, and progressive fibrosis. Concurrent presentation of EAF and GF suggests a pathogenetic link between them. OBJECTIVES: To identify histologic findings that tell them apart and construe the pathogenetic mechanisms behind each morphologic variable, 14 immunohistochemical markers were used to study the cells subpopulations in 14 cases of GF and 3 cases of EAF. MATERIALS AND METHODS: The lesions were classified according to their stage of development. The antibodies studied were: CD4, Foxp3, CD8, granzymes A and B, perforin, granulysin, CD20, CD56, CD68, ICAM-1, CD34, CD105, and 1A4. RESULTS: The intensity of the sclerotic response and the density of 1A4-immunostained cells were significantly higher in EAF. In both diseases, CD68 cells were the most numerous, followed by CD20, CD8, and CD4 cells. About 30% of cells expressed ICAM-1. Among cells with cytotoxic granules, granulysin-positive cells were the most frequent. CONCLUSIONS: Differences between GF and EAF were found to be mostly like due to anatomic site (usually skin of the face vs. sinonasal cavity) and stage of the disease development (usually earlier in cutaneous lesions because of their visibility). Innate and adaptive immunity, including B cells, T cells, and cytotoxic granules have a role in their pathogenesis.

TET2 Negatively Regulates Nestin Expression in Human Melanoma.

Although melanoma is an aggressive cancer, the understanding of the virulence-conferring pathways involved remains incomplete. We have demonstrated that loss of ten-eleven translocation methylcytosine dioxygenase (TET2)-mediated 5-hydroxymethylcytosine (5-hmC) is an epigenetic driver of melanoma growth and a biomarker of clinical virulence. We also have determined that the intermediate filament protein nestin correlates with tumorigenic and invasive melanoma growth. Here we examine the relationships between these two biomarkers. Immunohistochemistry staining of nestin and 5-hmC in 53 clinically annotated primary and metastatic patient melanomas revealed a significant negative correlation. Restoration of 5-hmC, as assessed in a human melanoma cell line by introducing full-length TET2 and TET2-mutated constructs, decreased nestin gene and protein expression in vitro. Genome-wide mapping using hydroxymethylated DNA immunoprecipitation sequencing disclosed significantly less 5-hmC binding in the 3' untranslated region of the nestin gene in melanoma compared to nevi, and 5-hmC binding in this region was significantly increased after TET2 overexpression in human melanoma cells in vitro. Our findings provide evidence suggesting that nestin regulation is negatively controlled epigenetically by TET2 via 5-hmC binding at the 3' untranslated region of the nestin gene, providing one potential pathway for understanding melanoma growth characteristics. Studies are now indicated to further define the interplay between 5-hmC, nestin expression, and melanoma virulence.

Keratoacanthoma and Keratoacanthoma-Like Squamous Cell Carcinoma: Similar Morphology but Different Pathogenesis.

Differential diagnosis between keratoacanthoma (KA) and squamous cell carcinoma (SCC) is difficult due to their similarities. The mechanisms that drive their distinct biological behavior are poorly understood. To investigate whether the assessment of microvessel density (MVD) could be helpful in KA and SCC differential diagnosis and to gain insight into the pathogenesis of KA-like neoplasms, we compared the density of CD105- and CD34-stained vessels in KAs and SCCs and their relation to the expression of the p53 oncoprotein and proliferation marker Ki67. This is an observational retrospective cohort study. Forty lesions with clinical appearance of KAs (29 KAs and 11 SCCs) entered the study. A biopsy was taken from each lesion at presentation and the natural clinical course was monitored for at least 1 month. Growing or minimally regressing lesions were submitted to complete surgical excision. The diagnoses were established on combined clinical, histological, and follow-up evaluations. The MVD and p53 or Ki67 expression in neoplastic cells were assessed through morphometry. The MVD did not show discriminating power between KAs and SCCs. The Ki67 proliferation rate was significantly higher in SCCs. Although neoangiogenesis (CD105-MVD) in KAs was associated with cell proliferation, in SCCs it was not. There was significant correlation between p53 expression and neoplasia size in SCCs but not in KAs. From our results, we may conclude that KA and SCC have similarities, as CD105- and CD34-MVD. However, the low Ki67 proliferation index and the positive correlation between Ki-67 index and neovascularization in KA suggest a dependence in neovascularization to grow in KA, pointing to involvement of distinct pathogenesis.

Identification of 2 novel ANTXR2 mutations in patients with hyaline fibromatosis syndrome and proposal of a modified grading system.

Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH) are rare, autosomal recessive disorders of the connective tissue caused by mutations in the gene encoding the anthrax toxin receptor 2 protein (ANTXR2) located on chromosome 4q21. Characteristically, these conditions present with overlapping clinical features, such as nodules and/or pearly papules, gingival hyperplasia, flexion contractures of the joints, and osteolytic bone defects. The present report describes a pair of sibs and three other JHF/ISH patients whose diagnoses were based on typical clinical manifestations and confirmed by histopathologic analyses and/or molecular analysis. A comparison of ISH and JHF, additional thoughts about new terminology (hyaline fibromatosis syndrome) and a modified grading system are also included.

Seminal vesicle invasion in radical prostatectomies: which is the most common route of invasion?

INTRODUCTION: Very few studies have been published on seminal vesicle invasion (SVI), and these have obtained conflicting results. The aim of the present investigation was to determine the most frequent of three possible routes of seminal vesicle invasion: (1) extraprostatic extension (EPE) into soft tissue adjacent to the seminal vesicle and then into the wall of the seminal vesicle, (2) invasion via the sheath of the ejaculatory duct, penetrating the muscular wall of the ejaculatory duct or extending up the ejaculatory duct into the seminal vesicle muscle wall, or (3) discontinuous metastases. MATERIALS AND METHODS: The surgical specimens of 230 consecutive patients submitted to radical prostatectomy were histologically evaluated by complete embedding and whole-mount processing. RESULTS: Of the surgical specimens obtained from 230 patients, 28 (12.17%) showed the presence of either unilateral or bilateral SVI. The routes of SVI in these 28 specimens were: (1) only via the sheath of the ejaculatory duct (0/28; 0%); (2) discontinuous metastases (3/28; 11%), (3) both EPE and via the sheath of the ejaculatory duct (6/28; 21%), and (4) only EPE (19/28; 68%). One-half (14/28; 50%) of the 28 seminal vesicles involved had unilateral invasion and, in most of these cases (42.85%), EPE was unilateral and ipsilateral. CONCLUSION: Our results suggest that the most important and most frequent route of SVI is extraprostatic extension of prostate carcinoma into the soft tissue adjacent to the ipsilateral seminal vesicle and then into the wall of the seminal vesicle.