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.

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.

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.

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.

Theory and practical application of superficial atypical melanocytic proliferations of uncertain significance (SAMPUS) and melanocytic tumours of uncertain malignant potential (MELTUMP) terminology: experience with second opinion consultation.

INTRODUCTION: The term superficial atypical melanocytic proliferations of uncertain significance (SAMPUS) is used to resolve discordance in diagnosis of "thin" melanocytic lesions. Melanocytic tumours of uncertain malignant potential (MELTUMP) is the descriptive term for an ill-defined group of dermal melanocytic tumours that exhibit features indicative of possible malignancy. We report our experience of collaboration with two leading international consultant pathologists in the diagnosis of melanoma in order to facilitate the practical application of the term SAMPUS and MELTUMP. METHODS: Twenty-seven cases of melanocytic lesions with interpretative problems were sent for consultation to Expert #1 (15 cases) and Expert #2 (12 cases). RESULTS: Two cases of MELTUMP and two cases of SAMPUS were diagnosed by Expert #1; three cases of MELTUMP and two cases of SAMPUS were diagnosed by Expert #2. Diagnosis was performed with H&E and molecular studies were not performed. DISCUSSION: Both experts included MELTUMP or SAMPUS atypical, ambiguous melanocytic lesions and melanomas. The diagnosis of SAMPUS and MELTUMP by consultant pathologists reflects the difficulty of classification with accuracy lesions that showed histological features of various atypical tumours or malignant melanoma. In these cases, biological potential may be established with molecular studies.

Squamous cell carcinoma arising in epidermal and human papillomavirus associated cysts: report of three cases.

OBJECTIVES: The clinical-pathological features of squamous cell carcinoma (SCC) arising in cutaneous cysts has been studied. METHODS: We report two cases of SCC arising in epidermal cyst (EC) and one case in human papilloma virus associated cyst (HPAC). RESULTS: In the first EC case, a 88-year-old man presented a cystic right zigomatic mass. Histopathology revealed a cyst lined by stratified squamous epithelium in continuity with invasive keratinizing SCC. In the second EC case, a 96-year-old man presented with a 1.5 x 1 cm nodular lesion localized at the helix of the right ear. Histopathology showed the typical cystic wall of an EC with transition to invasive keratinizing SCC. Finally, a 86 year-old woman presented with a perineal cystic nodule 1.5 cm in diameter. The wall showed varying degrees of papillomatosis, hypergranulosis, parakeratosis with dysplastic and koilocytic changes. Areas of in situ and invasive SCC were found. Human papillomavirus (HPV) 16 was detected. CONCLUSIONS: SCC arising in an EC may be diagnosed only with the support of an accurate histopathological documentation in order to exclude mimics. Regarding HPAC, the site, the malignant transformation and the finding of HPV 16 type, may be considered features of an extraordinary rare case.

Simultaneous occurrence of metastasizing carcinoid tumour of the gallbladder and chromophobe renal cell carcinoma in a young man.

Carcinoid tumour is an endocrine neoplasia described for the first time in 1888 and rarely observed in the extrahepatic bile ducts. Gallbladder carcinoid tumour was first reported by Joel in 1929. An endoluminal gallbladder lesion, with a bizarre echogenicity, and a mass in the upper pole of the left kidney were found in a 27 year-old man. The patient underwent a cholecystectomy with partial hepatectomy and a polar renal resection. Histological examination revealed a typical gallbladder carcinoid tumour with regional lymph nodal metastasis and a renal cell carcinoma, with morphological and histochemical features of the chromophobe type. This is a distinctive, rare variant, often described in the literature in association with other neoplastic and non-neoplastic diseases. To our knowledge, this is the first report of gallbladder carcinoid tumour with an unexpected aggressive behaviour in a very young patient, with concurrent renal cell carcinoma, chromophobe variant.

[Ovarian oxyphilic Sertoli cell tumor: case report and review of the literature]. / Tumore a cellule di Sertoli ossifile dell'ovaio: caso clinico e revisione della letteratura.

Ovarian oxyphilic Sertoli cell tumor is a rare neoplasm (only three cases were reported in literature). Sometimes the rarity itself of a lesion raises some problem in the diagnostics, especially if the case is send to several consultants. An unusual case of ovarian neoplasm came to our attention, and we sent some slides of the case to two well known referees of different Departments of Pathology. Pathologist 1 made a diagnosis of endometrioid adenocarcinoma, while Pathologist 2 made the diagnosis of oxyphilic Sertoli cell tumor. He sends the same slides to Pathologist 1, who confirmed his diagnosis. The two different diagnosis set different managements of the lesion for the clinician, but overall they set the pathologist who requested the consultation in a difficult position. In fact, when a pathologist sends to two experienced consultants a case, he really thinks to solve definitely the case itself. Unfortunately, sometimes it does not happen.

MELAS: clinical phenotype and morphological brain abnormalities.

We describe the clinical and neuropathological findings of three unrelated autopsy cases of MELAS harboring the A3243G transition in the mitochondrial DNA (mtDNA). Using immunohistochemical techniques, we studied the expression of several subunits of the respiratory chain in various brain regions from the same cases. In all three cases there was a reduced immunocytochemical staining for mtDNA-encoded subunits of the respiratory chain, confirming the presence of a defective mitochondrial protein synthesis in this disease. Mitochondrial abnormalities were mostly confined to multiple areas of different size and shape, in agreement with the focal character of the brain pathology in MELAS, and were most prominent in the cerebral cortex, providing a morphological contribution to the explanation of the cognitive regression of the patients. Immunoreactivity for mtDNA-encoded subunits was reduced in the walls of many pial and intracerebral arterioles of different brain regions but there was no clear correlation between territories of affected vessels and distribution of the histological and immunohistochemical lesions. Cerebral focal lesions in MELAS might have a metabolic nature and several pathogenetic mechanisms might be involved in the genesis of stroke-like episodes when there is a local increased ATP demand.

Prevalence of intestinal metaplasia in the distal oesophagus, oesophagogastric junction and gastric cardia in symptomatic patients in north-east Italy: a prospective, descriptive survey. The Italian Ulcer Study Group "GISU".

BACKGROUND: Incidence of adenocarcinoma of distal oesophagus and gastric cardia, probably arising from areas of intestinal metaplasia, has been increasing rapidly. AIMS: To define prevalence of intestinal metaplasia of distal oesophagus, oesophagogastric junction and gastric cardia and to evaluate potential associated factors, by means of a prospective multicentre study including University and teaching hospitals, and primary and tertiary care centres. PATIENTS: Each of 24 institutions involved in study enrolled 10 consecutive patients undergoing first-time routine endoscopy for dyspeptic symptoms. METHODS: Patients answered symptom questionnaires and underwent gastroscopy Three biopsies were taken from distal oesophagus, oesophago-gastric junction and gastric cardia, and were stained with haematoxylin and eosin. Specimens were also evaluated for Helicobacter pylori infection. RESULTS: A total of 240 patients (124 male, 116 female; median age 56 years, range 20-90) were enrolled in study. Intestinal metaplasia affected distal oesophagus in 5, oesophago-gastric junction in 19 and gastric cardia in 10 patients. Low-grade dysplasia was found at distal oesophagus and/or oesophago-gastric junction of 3/24 patients with intestinal metaplasia vs 2/216 without intestinal metaplasia (p<0.05). A significant association was found between symptoms and presence of intestinal metaplasia, regardless of location, and between Helicobacter pylori infection and intestinal metaplasia at oesophago-gastric junction. CONCLUSIONS: Intestinal metaplasia of distal oesophagus, oesophagogastric-junction and gastric cardia is found in a significant proportion of symptomatic patients undergoing gastroscopy and is associated with dysplasia in many cases. Although prevalence of dysplasia seems to decrease when specialized columnar epithelium is found in short segment, or even focally in oesophago-gastric junction, these small foci of intestinal metaplastic cells may represent source of most adenocarcinomas of cardia.

[Telemetric intraoperative diagnosis among hospitals in Trentino: first evaluations and optimization of the procedure]. / La diagnosi intraoperatoria telematica tra Ospedali in Trentino: prime valutazioni ed ottimizzazione delle procedure.

Telemetric, intraoperative frozen section diagnosis may be a useful tool for rural hospitals lacking an in-house pathology service. As a part of a Health Ministry Project on Telemedicine in Trentino (northern Italy), we developed a static telemicroscopy system (STeMiSy). This system connects the rural hospital of Cles with the main hospital of Trento. The two hospitals are 40 kilometers apart, and the road connecting the two towns runs across the mountains and has a heavy traffic. Before putting STeMiSy into practice, we tested the software and hardware on the LAN of the regional hospital system, by connecting the pathology services of Trento and Rovereto (20 kilometers apart). This test phase lasted three months and has not revealed major problems in the LAN nor in the robotic microscope, which was always precise and reliable. The quality of the images and the speed of transmission were largely sufficient for intraoperative frozen section diagnosis. Minor details of the histological slides were not always appreciated on the panoramic view. This loss of some details may be due to the quality of the panoramic view, which represents the 'surfing map' to read the cases. Nevertheless, the recognition of these small details was not so relevant as to change the surgical approaches. An audioconference system, utilizing the same transmission channel, not only slightly slowed the transmission but also caused some instability to the system. The audioconference system has therefore been abandoned, and when necessary we used the normal telephone. Macroscopic images of the whole surgical specimen, the surgeon's responsibility for the sampling, good technical quality of the slide, and good training will allow us to perform remote frozen section diagnosis in the absence of the pathologist. We believe that the main, and probably only, difficulty for this approach is not of a technical nature, but reflects the pathologist's resistance to making a remote video diagnosis.