Rosacea fulminans: two case reports and review of the literature.

Rosacea fulminans is a rare and severe inflammatory dermatosis which affects predominantly childbearing women. It is characterized by sudden onset and it usually localizes exclusively on the centrofacial areas, presenting with numerous fluctuant inflammatory nodules and papules which may coalesce. Treatment with isotretinoin in combination with topical and systemic corticosteroids is successful. Clearance of lesions may be obtained under systemic treatment with no or minimal scarring outcomes. Due to rare incidence its pathophysiological mechanisms, diagnosis and management remain controversial. We report two cases of rosacea fulminans arisen in otherwise healthy people and completely healed after treatment. Our aim is to share our experience about this disease in order to increase knowledge about its diagnosis, management and its treatment. We also make a review of the literature of this peculiar dermatosis.

Predictive value of the sentinel lymph node procedure in the staging of non-metastatic colorectal cancer.

PURPOSE: Despite the recent growing interest of the scientific community, there is still no consensus on the actual applicability and effectiveness of sentinel lymph node (SL) procedure in colon cancers. This study aims to quantify feasibility, detection rate, negative predictive value, and accuracy of the SL identified with fluorescent dye in early colon cancers (ECC). METHODS: This study conducted a consecutive sampling of 95 patients with non-metastatic colorectal cancer who have been treated with laparoscopic colon resection and complete mesocolic excision after a 25-mg indocyanine green peritumoral laparoscopic injection and SL identification with a near-infrared camera. The SL was later isolated and sent to ultra-staging. RESULTS: Ninety-five patients with an average age of 71 (range 37-90) and a mean BMI of 25 (range 18-39) have been recruited. On the patient sample (92 Pts), an average of 1.49 SL (range 1-5) and a mean time of 4 min were identified. The detection rate was 96.8% and the negative predictive value and accuracy rates were 96.2% and 93.4%, respectively. CONCLUSIONS: Mapping the SL with fluorescent dye can play an important role in the treatment of colon cancers, particularly those at early stages, and can lead to ultra-conservative surgery.

National survey of anatomical pathology centres in Italy: the questionnaire.

OBJECTIVES: To obtain a picture of the work done in Italian anatomical pathology centres in 2014, and evaluate differences between the various centres in terms of the workloads of medical and non-medical staff. METHODS: A self-administered questionnaire designed by a SIAPEC working group was e-mailed to 256 centres and subsequently collected by the Anatomical Pathology Service of Bolzano. QlikView software was used to prepare the final database and check the quality of the data, which were processed using version 18.0 of SPSS for Windows statistical software. RESULTS: The questionnaire was completed by 120 of the centres (46.9%), which were staffed by a mean number of 6.6 physicians (range 1-24), 1.6 biologists (range 0-7), 10.8 laboratory technicians (range 2-47) and 2.2 administrative personnel (range 0-9). During 2014, the centres carried out a mean of 15,000 histology examinations (range 3,215-50,680), almost 11,700 immunohistochemistry examinations (range 0-54,359), and a mean of 1,471 molecular biology examinations (range 0-31,322) relating to a mean of 704 patients (range 0-9,434), and a mean of 16,509 cytology examinations (range 0-150,000) relating to 13,383 patients (range 0-120,000). Each centre physician issued a mean of 2,444 histology examinations reports (range 613-11,000); the ratio between the number of immunohistochemistry examinations and the number of histology examinations was 0.8 (range 0-2.7); and each laboratory technician had a mean overall annual workload of 3,072 histology, molecular biology and cytology examinations (range 793-9,882/year). These values varied widely among the participating centres. The mean ratio between the number of histology examinations carried out and the number of physicians was 1,982.77:1 a year in the small centres (< 10,000 histology cases/year), 2,627:1 a year in the medium-sized centres (10-24,999 histology cases/year), and 2,881.34:1 in the large centres (> 25,000 histology cases/year). There were significant differences between the small and medium-sized centres (p = 0.004) and between the small and large centres (p = 0.001), but not between the medium-sized and large centres.The ratio between the total number of histology, molecular biology and cytology examinations and the number of laboratory technicians was 1,963.34 in the small centres (< 10,000 examinations/year), 2,717.11 in the medium-sized centres (10,000-24,999 examinations/year), and 3,531.56 in the large centres (≥ 25,000 examinations/year). There were significant differences between the small and large centres (p = 0.001) and between the medium-sized and large centres (p = 0.004), but not between the small and medium-sized centres. CONCLUSIONS: The data collected by means of this survey provide an important, albeit partial, point of reference concerning the status of Italian anatomical pathology centres and their recent, everyday working situation.

Predictive markers in lung cancer: a few hints for the practicing pathologist.

This review article highlights some important points in the evolving area of predictive biomarkers determination in non-small-cell lung cancer toward standardization of testing practices, including EGFR mutations, ALK and ROS1 rearrangements and immunohistochemical expression of PD-L1. Considerations for selecting appropriate populations for molecular testing, and emergence of other targetable molecular alterations are also discussed.

Metastatic malignant melanoma to the gallbladder. Case report and review of the literature.

Solitary metastasis of malignant melanoma (MM) to the gallbladder (GB) is rare and generally originates from skin melanoma. MM is a neoplasm with an often unpredictable course and metastases can potentially affecting all organs. The occurrence of metastasis in the GB is unusual and has only been exceptionally reported in the literature. We describe a case of an 86-year-old man with an isolated MM metastasis located within the GB presenting with symptoms mimicking acute cholecystitis. Anamnestically, he presented a history of malignant melanoma (Clark level III) resected from his left leg 17 years ago. Furthermore we provide a review of the literature with a focus on diagnostic clues to distinguish between primary versus secondary GB MMs and on the best surgical management that should be used.

Extra-nodal extension of sentinel lymph node metastasis is a marker of poor prognosis in breast cancer patients: A systematic review and an exploratory meta-analysis.

Invasive breast cancer is the most common malignancy in women. Its most common site of metastasis is represented by the lymph nodes of axilla, and the sentinel lymph node (SLN) is the first station of nodal metastasis. Axillary SLN biopsy accurately predicts axillary lymph node status and has been accepted as standard of care for nodal staging in breast cancer. To date, the morphologic aspects of SLN metastasis have not been considered by the oncologic staging system. Extranodal extension (ENE) of nodal metastasis, defined as extension of neoplastic cells through the nodal capsule into the peri-nodal adipose tissue, has recently emerged as an important prognostic factor in several types of malignancies. It has also been considered as a possible predictor of non-sentinel node tumor burden in SLN-positive breast cancer patients. We sought out to clarify the prognostic role of ENE in SLN-positive breast cancer patients in terms of overall and disease-free survival by conducting a systematic review and meta-analysis. Among 172 screened articles, 5 were eligible for the meta-analysis; they globally include 624 patients (163 ENE+ and 461 ENE-) with a median follow-up of 58 months. ENE was associated with a higher risk of both mortality (RR = 2.51; 95% CI: 1.66-3.79, p < 0.0001, I(2) = 0%) and recurrence of disease (RR = 2.07, 95% CI: 1.38-3.10, p < 0.0001, I(2) = 0%). These findings recommend the consideration of ENE from the gross sampling to the histopathological evaluation, in perspectives to be validated and included in the oncologic staging.

Double intestinal duplication and incidental neuroendocrine tumor of appendix, a rare case of acute abdomen.

INTRODUCTION: Intestinal duplication is rarely reported in adulthood and often remains undiagnosed until onset of complications. We describe the case of a 39 year old woman who came to our observation for acute abdomen due to a combination of double intestinal duplication (colon and ileum) and an incidental neuroendocrine tumor of the appendix. MATERIALS AND METHODS: A 39 year old woman who was admitted at with upper abdominal pain. Multisliced spiral CT scan showed a cystic lesion suggestive of an inflammed Meckel's diverticulum.The patient was underwent an urgent explorative laparoscopy. The intraoperative findings revealed a cystic lesion of the anti-mesenteric side of transverse colon, apparently dissectable from the bowel and a second lesion with a strongly adherent and unresectable from the anti-mesenteric aspect of the small bowel. A combined appendectomy was also performed. The histological diagnosis was consistent with a typical intestinal duplication for both intestinal lesionsand an incidental 2mm carcinoid tumor was also found in the appendix. The postoperative course was uneventful and the patient was discharged on p.o. day 5. At the presenttime she is well and following a regular oncologic follow-up. DISCUSSION: The rarity of this case is due to the concomitant presence of an incidental, sincronous, appendiceal NET. The elective treatment is surgical resection. CONCLUSION: Intestinal duplication in the adulthood is extremely rare and may either have an acute presentation as acute abdomen or represents an incidental finding of mass. We suggest that, once the diagnosis is suspected patient must undergo surgery.

Treatment of mild to moderate acne with a fixed combination of hydroxypinacolone retinoate, retinol glycospheres and papain glycospheres.

AIM: A fixed combination of 0.1% hydroxypinacolone retinoate (synthetic esther of 9-cis-retinoic acid), 1% retinol in glycospheres and 2% papain in glycospheres in aqueous gel has been recently introduced into the Italian market in order to reduce the incidence and severity of irritant contact dermatitis caused by topical retinoids, without compromising their efficacy. Primary objectives of this sponsor-free, pilot, open, multicenter study were to evaluate the efficacy and tolerability of this gel in patients with comedonal-papular, mild to moderate acne of the face. METHODS: Ninety-eight Caucasian patients (28 males and 70 females), with an age ranging from 15 to 40 years, were treated with the gel once daily for 12 weeks. Acne severity and treatment efficacy were evaluated by means of the Global Acne Grading System (GAGS) and lesions count. RESULTS: Ninety-four patients were considered evaluable. A 41% mean reduction in the GAGS score was observed; a 40.8% mean reduction of total lesions was recorded; 15.3% of patients experienced mild to moderate local side effects (dryness, peeling, erythema, burning). No patients stopped the treatment because of these side effects. CONCLUSION: This study, based on a high number of evaluable patients, demonstrates that this fixed combination is an effective and safe option for the treatment of comedonal-papular, mild to moderate acne of the face. A controlled clinical study is necessary to confirm these data.

Citrobacter koseri folliculitis of the face.

We report a case of severe Citrobacter koseri folliculitis of the face in a boy with acne. A 15-year-old boy affected by acne was admitted because of a rash located on the face. Dermatological examination revealed two large plaques, with numerous pustules, eschars and crusts, located bilaterally and symmetrically on the cheeks. Three bacteriological examinations were positive for C. koseri. The patient was successfully treated with i.m. ceftriaxone. C. koseri is a Gram-negative, aerobic, mobile, nonsporulating bacillus belonging to the Enterobacteriaceae family. It can cause meningitis, central nervous system abscess and sepsis, almost exclusively in infants and immunocompromised hosts. Respiratory tract and urinary infections have been reported in elderly people. Furthermore, rare cases of skin infections have been described.

Large cell carcinoma of the lung: clinically oriented classification integrating immunohistochemistry and molecular biology.

This study aimed at challenging pulmonary large cell carcinoma (LLC) as tumor entity and defining different subgroups according to immunohistochemical and molecular features. Expression of markers specific for glandular (TTF-1, napsin A, cytokeratin 7), squamous cell (p40, p63, cytokeratins 5/6, desmocollin-3), and neuroendocrine (chromogranin, synaptophysin, CD56) differentiation was studied in 121 LCC across their entire histological spectrum also using direct sequencing for epidermal growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and FISH analysis for ALK gene translocation. Survival was not investigated. All 47 large cell neuroendocrine carcinomas demonstrated a true neuroendocrine cell lineage, whereas all 24 basaloid and both 2 lymphoepithelioma-like carcinomas showed squamous cell markers. Eighteen out of 22 clear cell carcinomas had glandular differentiation, with KRAS mutations being present in 39 % of cases, whereas squamous cell differentiation was present in four cases. Eighteen out of 20 large cell carcinomas, not otherwise specified, had glandular differentiation upon immunohistochemistry, with an exon 21 L858R EGFR mutation in one (5 %) tumor, an exon 2 KRAS mutation in eight (40 %) tumors, and an ALK translocation in one (5 %) tumor, whereas two tumors positive for CK7 and CK5/6 and negative for all other markers were considered adenocarcinoma. All six LCC of rhabdoid type expressed TTF-1 and/or CK7, three of which also harbored KRAS mutations. When positive and negative immunohistochemical staining for these markers was combined, three subsets of LCC emerged exhibiting glandular, squamous, and neuroendocrine differentiation. Molecular alterations were restricted to tumors classified as adenocarcinoma. Stratifying LCC into specific categories using immunohistochemistry and molecular analysis may significantly impact on the choice of therapy.

Frequency of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from Trentino, North East Italy.

OBJECTIVE: Triple negative breast carcinomas (TNT) are infiltrating breast carcinomas (BC) with negative oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER-2) expression, and are associated with frequent BRCA1/BRCA2 mutations. The aim of the present study is to analyze the frequency and distribution of TNT in our population where a breast cancer screening program for women aged between 50 and 69 years is effective since 2001 with 85% accrual. METHODS: We investigated the records of 2112 consecutive BC and 153 interval BC (i.e. BC detected in the screened negative women in the interval between screening rounds). Tumours with complete negative expression of ER, PgR and Her2 were considered TNT; tumours with negative ER and PgR status and faint Her2 expression (score 1) were considered as possible TNT (pTNT). RESULTS: We identified 82 (3.8%) TNT and 20 (0.9%) pTNT in the series of 2112 consecutive BC and 7 TNT and 1 pTNT (5.2%) in the series of 153 interval BC. In the consecutive series, TNT/ pTNT were observed in 6.5% patients below 50 years and in 4.3% of patients above 50 years. A high proliferation rate (Ki-67 labelling > 36%) was observed in 87.8% of TNT (median labelling 56.3%) and in 60% of pTNT (median labelling 48.4%). CONCLUSIONS: Since TNT/pTNT occurring in women < 50 years is a criterion for selecting patients whom genetic counselling and BRCA1 testing should be offered, our study is of help in foreseeing the workload of the Unit of Medical Genetics and the Laboratory of Molecular Pathology.

Proliferative activity in human breast cancer: Ki-67 automated evaluation and the influence of different Ki-67 equivalent antibodies.

BACKGROUND: Ki67 labeling index (Ki67 LI), the percentage Ki67 immunoreactive cells, is a measure of tumor proliferation, with important clinical relevance in breast cancer, and it is extremely important to standardize its evaluation. AIM: To test the efficacy of computer assisted image analysis (CAIA) applied to completely digitized slides and to assess its feasibility in routine practice and compare the results obtained using two different Ki67 monoclonal antibodies. MATERIALS AND METHODS: 315 consecutive breast cancer routinely immunostained for Ki-67 (223 with SP6 and 92 with MM1 antibodies previously examined by an experienced pathologist, have been re-evaluated using Aperio Scanscope Xs. RESULTS: Mean human Ki67 LI values were 36%± 14.% and 28% ± 18% respectively for SP6 and MM1 antibodies; mean CAM Ki67 LI values were 31%± 19% and 22% ± 18% respectively for SP6 and MM1. Human and CAIA evaluation are statistically highly correlated (Pearson: 0.859, p<0.0001), although human LI are systematically higher. An interobserver variation study on CAIA performed on 84 cases showed that the correlation between the two evaluations was linear to an excellent degree. DISCUSSION: Our study shows that a) CAIA can be easily adopted in routine practice, b) human and CAIA Ki67 LI are highly correlated, although human LI are systematically higher, c) Ki67 LI using different evaluation methods and different antibodies shows important differences in cut-off values.

Small airways diseases.

The histopathology of the small airways is frequently quite subtle, even in cases with clinically severe disease. In the present paper, we will demonstrate some recognizable straightforward pathological changes in the small airways, and also provide a list of clinico-pathological conditions that should be considered when each is encountered. In the second part of the paper, we will briefly overview some general histological patterns of lesions and specific diseases that may involve the small airways. The basic lesions will be subdivided into inflammatory (acute, chronic, granulomatous, with or without necrosis), proliferative (epithelial or mesenchymal), and remodeling reactions. Inflammatory and proliferative reactions may lead to a the third category of remodeling reactions, characterized by a variety of distortions of normal bronchiolar architecture, including occlusion, constriction, dilatation (with or without mucostasis), tortuosity and nodularity. In addition to this schematic distinction, it is important to recognize that these lesions are frequently combined together and evolve with one another. Each of the 3 reaction patterns may be exquisitely bronchiolar, or may extend in the surrounding parenchyma. In this case, it is important to distinguish between lesions that extend from the bronchiole to the parenchyma or vice versa (such as in organizing pneumonia patterns, where the main lesion is in the parenchyma). As most of these lesions are part of a dynamic process, it is important to recognize that a single causative agent may produce distinct pathologic features at different times in the natural history of the disease. In addition, the same clinical disease may result in a variety of pathologic lesions. Accordingly, there may be not always be an unequivocal relationship between the clinical disease/condition and specific histopathologic lesions in the small airways.

Diffuse parenchymal lung diseases: when you see, think!

In this article, a series of tables (presented in alphabetic order) summarize the differential diagnosis of diffuse parenchymal lung diseases starting from the most frequent elementary lesions.

Sclerosing angiomatoid nodular transformation of the spleen associated with thrombocytopenia.

Sclerosing angiomatoid nodular transformation of the spleen, a recently described lesion of unknown pathogenesis, with a benign clinical course that is very often asymptomatic. Sclerosing angiomatoid nodular transformation may be a novo lesion or the final common pathway of various benign splenic conditions such as hamartoma, inflammatory pseudotumor and hemangioma. We report the case of a 68 year-old woman with thrombocytopenia and a splenic mass, diagnosed as sclerosing angiomatoid nodular transformation.

Multidisciplinary approach for in-deep assessment of joint prosthesis failure.

In spite of advancement in biomaterials and biomechanics, in development of new osteo-integrative materials and coatings, and in macro- micro- component design, a non negligible fraction of the implanted prosthesis fails before the expected lifetime. A prospective observational clinical study has been conducted to define and apply a set of experimental techniques to in-deep assess the failure of joint prosthesis. Microbiological, histological and micro-structural techniques were implemented to specifically address phenomena occurring at the tissue-implant interface. Results obtained from 27 cases of prosthetic joint failure are discussed in terms of sensitivity and specificity. A procedural flow-chart is finally proposed for the assessment of joint prosthesis failure.