Animal-Type Melanoma - a Mini-Review Concern-ing One of the Rarest Variants of Human Melanoma.

The authors declare they have no potential conflicts of interest concerning drugs, pro-ducts, or services used in the study. The Editorial Board declares that the manu-script met the ICMJE recommendation for biomedical papers. Submitted: 17. 6. 2017 Accepted: 1. 11. 2018.

AJCC 8th Edition (2017) versus AJCC 7th Edition (2010) in thin melanoma staging.

In comparison with the 7th Edition, the 8th Edition of the American Joint Committee on Cancer (AJCC) staging system no longer considers the mitotic count in the a or b T1 categorization for melanoma, but it adopts a sub-stratification based on the Breslow's depth. Today, the death burden of thin melanoma is still severe, despite of attempts for early screening. We believe that a bio-histological implementation may explain this evidence. It is generally accepted that melanoma progression includes two subsequent phases: the radial growth phases (RGP) and the vertical growth phase (VGP). If left untreated, RGP is able to move towards VGP. In this second phase, melanoma grows as a malignant, mitotically active, tumor with invasive and metastatic capacities. By our experience, thin melanoma includes three bio-histological subtypes: the non-tumorigenic micro-invasive RGP without significant regression, the micro-invasive RGP with regression of uncertain tumorigenic potential at diagnosis, due to the extensive presence (> 75%) of regression which could contain a VGP clone, and the micro-invasive tumorigenic VGP. Therefore, we are prone to support that the prognosis of thin melanoma is correlated with the type of growth phase inside it.

Exploring the mesenteric lymphatic apparatus: A morphological and immunohistochemical investigation with clinical correlations.

Modern immunohistochemical techniques allow a detailed study of the lymphatic system in many organs and areas of the body. We performed an in-depth study on lymphatic vessels of the ileal and colonic mesenteries, together with the greater omentum where they appear particularly numerous and mainly represented by capillaries interconnected among themselves and with lymph nodes. The capillary wall consists of a fine single sheath of endothelial cells wrapped around by a subtle collagen membrane and deprived of valves. The progression of lymph flow is promoted by external forces acting on the capillary walls. Only at the mesenteric roots can pre- and post-lymph nodal collector vessels be observed. Our observations help to explain different patho-physiological correlations and the possible presence of skip lymph node metastases.

Deep inside of gastric signet-ring cell carcinoma.

The histology of signet-ring cell carcinoma (SRC) of the stomach has been revisited with the support of current immuno- histochemical techniques in order to explain particular features of this tumor; its great capacity of local diffusion and lymph node metastasis, also through a neo-lymphoangiogenesis. An observational retrospective study on 50 cases of SRC in stage II and III has been performed with the addition of histochemical (Alcian Blue, DDD-Fast Blue B, Mercury Orange) and immunohistochemical (cytocheratin, CD3, CD4, CD8, CD10, CD56, CD68, perforin, granzyme B, podoplanin, collagen type IV) investigations for each case. The signet ring cells, typical for this tumor, show abundant content of electro-negative sialomucins and demonstrate a great capacity of diffusion through the gastric wall. They evoke production and deposition of collagen type IV in the sub-mucosa layer through the local action of fibroblasts. The immunological response to this tumor in the gastric wall and in the metastatic lymph nodes is represented by an increase of B and T-helper lymphocytes, but not of T-killers or natural killers. The neoplastic cells are curiously able to avoid these newly formed 'lymph nodules'. An extended neo-lymphangiogenesis has been observed around the primary tumor and in metastatic lymph nodes. A careful immunohistochemical characterization has allowed a better knowledge of SRC, regarding especially the peculiar behavior of local diffusion of its cells, the associated neo-lymph angiogenesis, and poor immunological reaction.

Mitochondrial DNA content: A new biomarker for sudden intrauterine unexplained death syndrome (SIUDS).

In literature there are no data related to mitochondrial DNA (mtDNA) content in sudden intrauterine unexplained death syndrome (SIUDS). To test the hypothesis that a quantitative excess of mtDNA could play a role in the pathogenesis of SIUDS, mtDNA content was measured in cerebral cortex of 9 SIUDS and in 7 controls. The median (interquartile range) mtDNA in SIUDS and controls was 14,000 (8600-33,500), 3400 (0-8500) copies per nuclear DNA, respectively (p=0.007). If mitochondria are involved in SIUDS, then higher mitochondrial DNA content may be a biomarker of this syndrome.

Image-Guided Proper Liver Segmentectomy.

BACKGROUND: The new cross-sectional radiological tools, 3D computed tomography and magnetic resonance, allow a precise study of the liver anatomy. Thanks to these imaging techniques, a new space inside the liver parenchyma, the "hepatic core," was recently recognized, where the hila of liver segments are present. METHODS: On the basis of anatomical and radiological observations, we identified a new virtual plane of dissection, named "hepato-portal," which is useful in liver segmentectomy, if integrated with the classical planes of dissection. RESULTS: Simulated surgical procedures can be intra-operatively transferred by ultrasounds. In this way, we performed ten "proper" liver segmentectomies through preliminary sections of the hilar vessels and a precise dissection of the boundaries of each segment. CONCLUSIONS: Our experience underlines the value of integrating anatomy and radiology in the simulated liver surgery.

SAMPUS, MELTUMP and THIMUMP - Diagnostic Categories Characterized by Uncertain Biological Behavior.

In the dermatopathological practice, there is a group of atypical melanocytic lesions with borderline histological features between benign simulants and malignant melanoma (MM), due to conflicting diagnostic criteria and inter-observer disagreement. In these cases, the dermatopathologist is authorized to seek consult with an established expert in the field, but even the most experienced specialist may not be sure about the correct diagnosis and the subsequent biological behavior. There is general consensus among qualified dermatopathologists that can be helpful to insert these ambiguous cases into two diagnostic categories: SAMPUS (Superficial Atypical Melanocytic Proliferations of Unknown Significance) and MELTUMP (MELanocytic Tumors of Uncertain Malignant Potential). According to the conception of MM progression through two phases, the radial growth phase and the vertical growth phase, it is possible to identify a novel subtype of thin melanoma (THIM) with uncertain metastatic potential, due to the presence of extensive regression ( 75% of the lesion volume), which we here define with the acronym THIMUMP (THIn Melanoma of Uncertain Metastatic Potential) for the first time in literature.Key words: malignant melanoma - thin melanoma - histology.

Neurodevelopmental disorders and pesticide exposure: the northeastern Italian experience.

Endocrine disruptors are chemical substances that can interfere with the endocrine system. They include pesticides, metals, additives or contaminants in food, and personal care products. Pesticides are the only substances intentionally released into our environment to kill living things (herbicides, insecticides, fungicides, rodenticides). There is scientific evidence that exposure to pesticides produces a growing number of human pathological conditions; among these, stillbirth is an emerging issue.

New advances on placental hydrops and related villous lymphatics.

Fetoplacental hydrops is the final stage of several pathological conditions in which the placenta and umbilical cord become edematous and the fetus develops an anasarcatic state characterized by an excessive accumulation of extravascular fluids in at least two serous cavities of the body. It is a common histological finding of stillbirth, characterized by the appearance of markedly edematous villi, suggesting an increased interstitial fluid accumulation. The recent improved knowledge of lymphangiogenesis and the availability of monoclonal antibodies selectively labeling lymphatic endothelium lead to the hypothesis that villous edema is essentially a lymphedema from defective lymphatic function following inadequate villous blood circulation. Lymphedema is a morphologic phenotype found by our research group in a 24-case series of stillbirths from different morbid conditions such as chromosomal aberrations, congenital malformations, inherited hemoglobinopathies, and prolonged perinatal severe anoxia. Unlike long-lived organs, the placenta is devoid of innervation by the autonomic nervous system; therefore, the vascular tone regulation and the peripheral perfusion are modulated by the expression of the angiotensin converting enzyme (ACE) in the vascular endothelia. This finding may suggest to the clinician to search for a more suitable therapy in case of mother's hypertension during pregnancy.

Pre-miR146a expression in follicular carcinomas of the thyroid.

INTRODUCTION: Micro-RNA, a new class of small, non-coding RNAs, have been shown to be deregulated in several human carcinomas. In particular, SNP rs2910164 in pre-miR146a appears to be correlated with papillary thyroid carcinoma and may be involved in its genetic predisposition. Since data on follicular thyroid carcinomas (FTC) are lacking, we evaluated the involvement of SNP rs2910164 in FTC. METHODS: Thirty-nine cases of FTC and 20 follicular adenomas, defined according to WHO criteria, were selected. DNA and RNA were extracted from formalin-fixed paraffin-embedded blocks of both neoplastic and non-neoplastic areas. The DNA region of pre-miR146a, containing SNP rs2910164, was sequenced. Total RNA including miRNAs was used for stem-loop RT reactions, and applying a standard TaqMan PCR kit protocol for real-time PCR. Wilcoxon signed-rank test and Friedman test were used for statistical analyses. RESULTS: In 31% of FTC, the G allele was observed in neoplastic tissues, compared with the non-neoplastic areas (p < 0.05), whereas the CC phenotype was completely absent in tumours. Moreover, the expression of pre-miR146a was found to be significantly down-regulated in neoplastic tissues from FTC cases (p = 0.043), although no significant differences were seen in follicular thyroid adenomas. DISCUSSION: The expression profile of pre-miR146a can be correlated with FTC tumourigenesis. The G allele in SNP rs2910164 appears to be correlated with the transition from normal to neoplastic tissue. The GG and GC alleles appear to be associated with an increased risk for FTC, while the CC allele seems to play a protective role.

[Biological characterization of metastatic renal cell carcinoma]. / Caratterizzazione biologica del carcinoma renale metastatico.

Renal cell carcinoma is the sixth leading cause of death for cancer in industrialized countries and one third of patients has metastases at the time of diagnosis. The three most common histological types of renal cell carcinoma are: clear cell carcinoma (70-80%), papillary carcinoma (10-15%) and chromophobe cell carcinoma (5%). The location of metastases vary according to histotype: lung metastases are found in 53.6% of cases in patients with clear cell carcinoma, whereas in patients with papillary carcinoma or chromophobe cell carcinoma in 33.3% and 28.2% of cases, respectively. In contrast, chromophobe cell carcinoma is more often associated with liver metastases (33.3%), compared with clear cell carcinoma (9.7%) or papillary carcinoma (18%). Patients with renal cell carcinoma metastatic to a single organ have a better prognosis than patients with metastases in multiple organs and the overall survival of patients with localized lung metastases is similar to that of patients with exclusive bone metastases. The overall survival, therefore, is related more to the number of organs involved by metastasis rather than by the location of metastases. The widespread use of abdominal non-invasive diagnostic procedures, with an incidental finding of renal cell carcinomas still in a low stage of development, and the refinement of surgical techniques for resection of metastatic disease (metastasectomy) have led to only a slight improvement in overall survival in the last 30 years for the resistance of the tumor to common chemo-radiotherapy. Surgery remains the best therapeutic option and a rising in cutting-edge molecular therapies is strongly needed.