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This case was presented at the on-line meeting on the ADOI platform held on Dicember 15th 2021 by Dr Boggio.

Prof. Raffaele Gianotti (“Raf” for friends) was born on July 7th,1959 in Milan (Italy). His father, Prof. Ferdinando Gianotti (1920-1984), was a famous pediatric dermatologist that gave his name to the “papular acrodermatitis of childhood” (Gianotti-Crosti Syndrome) [...].

Paraffin embedding of small, thin tissue samples requires specific expertise for optimal orientation before tissue sectioning. This study evaluates the real-life utility of the agar pre-embedding technique for small skin biopsies with regards to lengthening of work times, problems in orientation (re-embedding) and ancillary techniques (immunohistochemistry and in situ hybridisation) between two high work flow pathology laboratories, one of which routinely uses the agar pre-embedding technique and one which does not. The mean time required for pre-embedding in agar was 30.4 s, but time for paraffin embedding for agar pre-embedded samples was shorter than the traditional method (177 vs 296 s; p

Background: Multiple studies have compared the performance of artificial intelligence (AI)–based models for automated skin cancer classification to human experts, thus setting the cornerstone for a successful translation of AI-based tools into clinicopathological practice. Objective: The objective of the study was to systematically analyse the current state of research on reader studies involving melanoma and to assess their potential clinical relevance by evaluating three main aspects: test set characteristics (holdout/out-of-distribution data set, composition), test setting (experimental/clinical, inclusion of metadata) and representativeness of participating clinicians. Methods: PubMed, Medline and ScienceDirect were screened for peer-reviewed studies published between 2017 and 2021 and dealing with AI-based skin cancer classification involving melanoma. The search terms skin cancer classification, deep learning, convolutional neural network (CNN), melanoma (detection), digital biomarkers, histopathology and whole slide imaging were combined. Based on the search results, only studies that considered direct comparison of AI results with clinicians and had a diagnostic classification as their main objective were included. Results: A total of 19 reader studies fulfilled the inclusion criteria. Of these, 11 CNN-based approaches addressed the classification of dermoscopic images; 6 concentrated on the classification of clinical images, whereas 2 dermatopathological studies utilised digitised histopathological whole slide images. Conclusions: All 19 included studies demonstrated superior or at least equivalent performance of CNN-based classifiers compared with clinicians. However, almost all studies were conducted in highly artificial settings based exclusively on single images of the suspicious lesions. Moreover, test sets mainly consisted of holdout images and did not represent the full range of patient populations and melanoma subtypes encountered in clinical practice. info:eu-repo/semantics/publishedVersion

Journal of the American Academy of Dermatology : JAAD 86(3), 640-642 (2022). doi:10.1016/j.jaad.2021.02.009, Published by Elsevier, Amsterdam [u.a.]

Myoepithelioma is a rare salivary tumour which is usually encountered in the parotid gland. Outside the parotid, myoepithelioma may arise from minor salivary glands of the hard palate and less frequently in bronchi or breast. In this report we describe the unique case of a metachronous bilateral nasopharyngeal myoepithelioma arising from the tubaric regions. Its microscopic features, immunophenotype, and the differential diagnosis together with a review of literature are discussed.

Thirteen melanocytic skin neoplasms with a consultation diagnosis by A. Bernard Ackerman were submitted to immunohistochemistry for HMB-45, Ki67, cyclin D1, e-cadherin, and p16; 9/13 cases underwent fluorescence in situ hybridization (FISH) test targeting 6p25 (RREB1), 6q23 (MYB), centromere 6 (Cep6), and 11q13 (CCND1), as well as the centromere 7 (Cep7). A “consensus diagnosis” among 3 experts was also advocated both before and after morphomolecular information. Three neoplasms with a consultation diagnosis of Spitz nevus showed at least 3 abnormal immunohistochemical patterns; 2 of these cases were also FISH-positive for CCND1 gain, but none of them had a final consensus diagnosis of melanoma. Two neoplasms with a consultation diagnosis of congenital nevus received a consensus diagnosis of melanoma. Molecular morphology techniques can highlight the atypical features of melanocytic neoplasms and support existence of a morphobiologic “spectrum”: This should be mirrored in the final report by abandoning the dichotomic (benign vs malignant) diagnostic approach.

Serum HER-2/neu concentrations were evaluated in 172 healthy subjects, 176 primary and 55 metastatic breast cancer patients, employing a new automated assay (Bayer Immuno 1™ serum HER-2/neu). Using 13 ng/mL as the cutoff, abnormal HER-2/neu serum levels were found in 8% (14/176) of primary and 50.9% (28/55) of metastatic breast cancer patients. Both in primary and metastatic breast cancer a significant relationship was found with the stage of the disease when serum HER-2/neu was considered as a categorized variable (p=0.0003 and p=0.02, respectively), but not when it was taken as a continuous variable (p=0.247 and p=0.146, respectively). Moreover, we evaluated the correlation between Immuno 1™ HER-2/neu and Oncogene Research Products ELISA assay in 53 normal subjects, 46 primary and 34 metastatic breast cancer patients. The correlation was relatively good (p

Very few areas in the realm of diagnostic dermatopathology may be so challenging both for the dermatologist and the histopathologist as are those related to panniculitis, because of their frequent overlapping microscopical patterns and uncertain etiology. Classically, a dicotomic taxonomy key has been proposed according the prevalent involvement of subcutaneous septa or lobules of the inflammation, presence or absence of vasculitis and type of vessel involved, but exceptions to this approach do occur and overlapping forms are sometimes encountered. Infectious panniculitides have also been traditionally approached according to this schema, and their microscopic diagnosis may be even more complex when the causative agent is unknown and underrepresented in the specimen. Many types of pathogens are capable to evoke protean clinical manifestations, which range from organism-specific to aspecific pictures. For this reason a tissue biopsy is always mandatory to ascertain the type of lesion and differentiate an infectious process from its many other mimickers essentially represented by reactive-based panniculitides. Recognition of morphologic changes which characterize distinct infections in the subcutis often needs a complete clinical history, physical examination and laboratory studies, especially when few microorganisms if any are found. This review will be focussed on the pathophysiology of the adipose tissue in relation to immunity and mechanisms of host reaction. The most frequent infectious panniculitides will then be discussed with special reference to their microscopic pictures, to provide clues to their specific diagnosis and the use of immunohistochemistry and molecular biology techniques as ancillary techniques.

Hormonal manipulation has been proposed as a possible new approach to the treatment of pancreatic cancer. We studied the effect of orchiectomy and testosterone replacement on early stage pancreatic carcinogenesis induced by diisopropanolnitrosamine (DIPIN) in Syrian golden hamsters. Eighty-five hamsters (mean body weight, 100 g) were divided into the following treatment groups: 1) DIPN (n = 20); 2) DIPN plus orchiectomy (n = 17); 3) DIPN plus orchiectomy plus testosterone (n = 18); 4) orchiectomy (n = 10); 5) sham operation (n = 10); 6) DIPN plus testosterone (n = 10). DIPN (125 mg/kg/body wt.) was administered s.c. every week and testosterone propionate (10 ng/g) was administered s.c. every 3 weeks. Bilateral orchiectomy was performed 1 week after the first injection of DIPN. All animals were killed 15 weeks after starting the treatment. The whole pancreas was removed, weighed and histologically examined. There was no difference in the incidence of preneoplastic lesions among groups 1, 2, 3 and 6 (respectively 87%, 83%, 77% and 80%); 3 animals in each group developed invasive carcinoma. In control groups (4 and 5), no precancerous lesions were recorded. In this experimental model, orchiectomy and testosterone replacement had no effect on nitrosamine-induced pancreatic carcinogenesis.

The authors value the distribution of some parameters such as age, sex, life habits, kind of clinical diagnosis and its relation to histological diagnosis in a population of 110 patients heterogeneous for rank and provenance. After describing the kind of casualty department aid, they explain the meaning of the word leukoplakia and underline the difficulties of clinical diagnosis: the macroscopic appearance of the white patch (according to WHO definition) is often comparable to other oral diseases either classified as precancerous lesions or not.

Serous cystic neoplasms of the pancreas are uncommon tumors classified as microcystic adenomas. In this article, the authors report clinico-pathologic features of seven cases of macrocystic variant of the serous cystadenoma.Seven patients (5 females and 2 males) with a diagnosis of cystic lesion of the pancreas were observed after 1995. Clinical, radiological, and pathologic features, including immunohistochemistry, were reported. Enzymes and tumor markers CEA, CA 19-9, CA 125, CA 15-3, CA 72-4, and mucin-like carcinoma-associated antigen (MCA) were investigated in the serum and cyst fluid of the patients. Cytology was also performed.Six patients were symptomatic complaining abdominal pain. All cases had radiologic evidence of unilocular cyst of the pancreas. The suspected diagnosis was consistent with mucinous cystic neoplasm. Serum tumor markers were all in the normal range. After surgery, pathology showed in all cases a cyst lined with cuboidal, periodic acid-Schiff (PAS)-positive epithelium, without mucin content or atypia. Minute microcysts were found surrounding the main cavity. Immunohistochemical stains were positive for cytokeratin, CA19-9, CA15-3, CA 72-4, and MCA. CEA was unexpressed. CA 125 in the cyst fluid were found elevated in three cases and CA 19-9 in three cases. Cytology was negative in all cases.When a unilocular pancreatic cyst is found, without history of pancreatitis and gallstones, having low serum tumor markers levels and negativity of CA 72-4 and MCA in the cyst fluid, the diagnosis of the macrocystic variant of the serous cystadenoma may be suggested. At present, the diagnosis is still based on pathological examination after cyst removal.

Solitary true cysts of the pancreas are extremely rare: to date, only eight cases have been reported in the English literature, four of which had clinical significance. An additional three cases of solitary true cysts of the pancreas are presented. One patient was incidentally found at operation, performed for other disease, to have a cystic lesion in the body of the pancreas; the other two patients experienced abdominal pain and nausea. Abdominal US, CT, and MR showed a unilocular cyst in the body and tail of the pancreas. In both cases, preoperative diagnosis of pancreatic cystic neoplasm was made. Two patients underwent excision of the mass and one distal pancreatectomy. Analysis of the cyst fluid revealed high CA 19-9 levels in two and CA 125 levels in one case. All cysts were lined by cuboidal epithelium, without morphological alterations. Preoperative differential diagnosis with the most common cystic pancreatic lesions (inflammatory or neoplastic) is difficult.

A case of cor triatriatum in a 66-year-old man is reported. The patient died of pneumonia; ante mortem diagnosis was made with both transthoracic and transesophageal echocardiography. Autopsy finding showed a very good correlation between anatomical and echocardiographic abnormalities. Cor triatriatum is amenable to surgical correction and echocardiography is extremely helpful in the diagnosis.

The effects of the cholecystokinin (CCK)-analogue, caerulein, and CCK-receptor antagonist lorglumide (CR-1409) on pancreatic carcinogenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA) were studied. One hundred thirty rats were divided into the following 10 treatment groups: group 1, DMBA (2-3 mg); group 2, DMBA + caerulein (5 micrograms/kg); group 3, DMBA + caerulein + CR-1409 (12 mg/kg); group 4, caerulein + DMBA; group 5, caerulein + CR-1409 + DMBA; group 6, DMBA + CR-1409; group 7, CR-1409 + DMBA; group 8, caerulein; group 9, CR-1409; and group 10, sham operation + saline. DMBA was surgically implanted into the pancreas. Caerulein and/or CR-1409 was administered twice daily for 15 days after (in groups 2, 3, and 6) or before (in groups 4, 5, and 7) DMBA implantation. Six months after carcinogen administration, all rats were sacrificed and autopsied. The incidence of pancreatic cancer appeared significantly (P < 0.001) increased when caerulein was administered following DMBA implantation. CR-1409 significantly inhibited (P < 0.02) caerulein effects and reduced tumor growth when injected after carcinogen exposure.

Osteoma is a benign bone tumour with a very slow growth. In the maxillofacial district the paranasal sinuses and the mandible are more frequently involved. This type of tumour is clinically asymptomatic and the signs of its presence are due to the fact that its expansive and centrifugal growth changes the face features. The surgical operation has a double aim: to solve the aesthetic problem and to prevent complications. In fact, obstructions and compressions ab estrinseco may compromise the function of the nearest organs. The aim of our work has been to show a clinical case which is interesting from a clinical, diagnostic and therapeutic point of view.

Background Several studies have shown that the main circulating biomarkers of liver and colorectal cancer can be detected in the bloodstream and are also associated with immunoglobulin M to form stable complexes. These immune complexes show increased capacity of discrimination between cancer patients and healthy controls if combined with the free biomarker form. Within the context of the Project FIRB 2003 - Nanosized Cancer Polymarker Biochip - we wanted to investigate if IgM complexes have importance also in breast cancer. We focused our study on the immune complexes between IgM and CA 15.3 because free CA 15.3 is the most commonly used breast cancer biomarker in clinical practice. However, this biomarker alone lacks satisfactory sensitivity especially in early cancer detection. Aim The aim of our study was to assess the occurrence of immune complexes between CA 15.3 and IgM in sera from patients with primary breast cancer and in sera from healthy controls to evaluate its putative diagnostic value compared with the diagnostic value of free CA 15.3. Methods A total of 130 serum samples were obtained from 56 healthy women (mean age±SD, 45±8.23 years) and 74 women with stage l and II breast cancer (mean age±SD, 59±13.6 years) before any treatment, either surgical or chemo-therapeutic. Serum samples were collected, aliquoted and stored at-80°C in the centralized biobank of the project according to very stringent standard operating procedures (SOPs) distributed by the coordinating unit. To evaluate the presence of CA 15.3-lgM immune complexes, we developed and validated a novel enzyme-linked immunosorbent assay (ELISA) with a polyclonal rabbit anti-human CA 15.3 antibody (Abcam) as the catcher antibody. CA 15.3-lgM was detected with peroxidase-conjugated anti-human IgM and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydrogen peroxide as substrate (Sigma Aldrich, Italy). The levels of CA 15.3-lgM were expressed in arbitrary units per mL (AU/mL) by interpolation on a calibration curve obtained by serial dilution of a reference calibrator purified by gel filtration chromatography from a pool of serum samples with high levels of CA 15.3-lgM. Serum levels of free CA 15.3 were assessed in parallel on each sample using an automated immunoassay system (ADVIA Centaur-Siemens Diagnostics) and expressed in U/mL. Results To discriminate between cancer patients and healthy controls, we used as cutoff values 31.5 U/mL for free CA 15.3 (corresponding to the cutoff used in the clinical routine) and 794 AU/mL for CA 15.3-lgM (representing the 95th percentile of the distribution of serum levels of CA 15.3-lgM in healthy controls). By using these cutoff values, we obtained a sensitivity of 1 0% (7/74 cases) and a specificity of 95% (53/56 controls) for CA 15.3-lgM. The sensitivity and specificity of free CA15.3 were 7% (5/74 cases) and 1 00% (56/56 controls), respectively. Interestingly, the serum levels of the two biomarkers did not overlap, so their combination at 95% specificity identified 12/74 cases (16.2%). When we took a cutoff of 22 U/ mL for free CA15.3 (the 95th percentile of its distribution in healthy controls), we calculated a sensitivity of 26% (1 9/74 cases) and a specificity of 95% (53/56 controls); its combination with CA 15.3-lgM had a sensitivity of 34% (25/74 cases) and a specificity of 90% (50/56 controls). Conclusions These results demonstrate for the first time the presence of CA 15.3-lgM in the bloodstream of patients with breast cancer. In addition, our data suggest that CA 15.3-lgM is a complementary serological marker to free CA 15.3 and the combination of these biomarkers could improve the diagnosis of breast cancer.