Tumour infiltrating lymphocytes and PD-L1 expression as potential predictors of outcome in patients with malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare and aggressive form of tumour. Some mesotheliomas have been proven to be highly immunogenic. Here, we investigated the correlation between tumour infiltrating lymphocytes (TILs) or programmed cell death ligand 1 (PD-L1) expression with overall survival (OS) in patients with MPM. 62 Paraffin-embedded formalin fixed (PEFF) samples were analysed for TILs and PD-L1 expression. Patients were divided in 4 groups according to a cut-off of the percentage of TILs found per sample as measured by immunohistichemistry: "0" or absent (between 0 and 5%), "1" or low (between 6 and 25%), "2" or moderate (between 26 and 50%) and "3" or high (between 51 and 75%). OS was then correlated with different TILs' expression patterns. Moreover, PD-L1 expression was assessed within the tumour as well as in the adjacent stroma on the same samples. Higher expression of peritumoral TILs (Group 2 + 3) versus Group 0 and 1 correlated with improved OS (p-value = 0.02). On the contrary PD-L1 expression seemed to be inversely correlated with clinical outcomes, even in the absence of statistical significance (HR 1.76; p = 0.083 95% IC 0.92-3.36 in areas within the tumour; HR 1.60; p = 0.176 95%; IC 0.80-3.19 in areas within the stroma). No relationship between TILs and PD-L1 expression was identified. Our research supports the use of TILs and PD-L1 expression as potential outcome predictors in patients with MPM. The use of TILs and PD-L1 as biomarkers for checkpoint inhibitors' efficacy warrants future investigation.

Verruciform xanthoma of the oral mucosa. Report of a case.

Verruciform xanthoma is a rare benign lesion of unknown etiology and pathogenesis, although an inflammatory process seems to be implicated in its origin. It usually shows a slow-growing small lesion which can be sessile or pedunculated and has a typical rough and granular surface. A clinical case of an asymptomatic verruciform xanthoma of the ventral surface of the tongue in a 24-year-old male is reported. The lesion was noticed for the first time during a routine dental examination and it appeared as a sessile whitish verrucous lump hard in texture. An incisional biopsy followed by the excision of the whole lesion was performed. The histological and immunohistochemistry examinations were carried out using antibodies CD68-KP1, CD68-PGM1, alpha-1-antitrypsin and vimentin, desmin, cytokeratins, NSE and S-100. Histology showed epithelial degeneration. The connective tissue papillae were entirely occupied by foamy cells that were positive for CD68-KP1, CD68-PGM1, alpha-1-antitrypsin and vimentin and negative for desmin, cytokeratins, NSE and S-100. The foamy cells were characterized by a large granulous cytoplasm and small picnotic nuclei. In accordance with the literature, the immunohistochemistry analysis confirmed that foamy cells are likely to have a macrophagic origin and that epithelial degeneration could be correlated with the pathogenesis of this lesion.

Masson's pseudoangiosarcoma, alias intravascular papillary endothelial hyperplasia, in dissecting aortic aneurysm caused by cystic medionecrosis.

This report describes a 25-year-old man who died due to extensive cystic medionecrosis of the aortic wall complicated by both an acute and an ancient dissection. The very unusual finding of an intravascular papillary endothelial hyperplasia, also known as Masson's pseudoangiosarcoma, in the dissected wall is reported given its resemblance to a hemangiosarcoma.

Cutaneous pseudolymphoma of the breast with late homozonal relapse.

Cutaneous pseudolymphomas refer to a group of lymphoproliferative disorders of difficult classification and diagnosis. Considered as very low-grade lymphomas by some authors, they are actually able to progress to overt cutaneous lymphomas in a minority of cases. We report a case of cutaneous pseudolymphoma of the breast in a 21-year old woman which relapsed locally ten years later. The case is of interest for the unusual localisation of the lesion, for its recurrence after such a long period of time, and for the homozonal site of recurrence. The reported features support both the long course and the lymphomatous nature of such lymphocytic proliferations.

Malignant pleural mesothelioma following chemotherapy for breast cancer.

Although the induction of malignant mesothelioma by radiotherapy, used alone or in combination with chemotherapy, has been previously reported in the literature, the number of documented cases is extremely small. We report a case of malignant pleural mesothelioma arising four years after chemotherapy for breast cancer in a 42-year-old woman without a history of exposure to asbestos. To our knowledge, this is the f rst reported case of malignant pleural mesothelioma following treatment with chemotherapy alone. It is of interest not only for the patient's young age and the absence of exposure to asbestos, but also for the very short latency period, if compared with asbestos-related mesothelioma.

Gastric epithelium proliferation in early Hp+ and Hp- gastritis: a flow cytometry study.

BACKGROUND: Helicobacter pylori increases cellular turn-over causing hyperproliferation and possible assumption of neoplastic characteristics by the gastric epithelial cells. To verify whether patients at risk of cancer can be identified at the very first stages of gastric disease, we studied a sample of patients affected by early Hp+ and Hp- gastritis by flow cytometry and assessed the methods commonly adopted to study gastric cell proliferation. METHODS: 48 fresh biopsies taken from the gastric antrum and body of 24 patients who had undergone endoscopy for dyspepsia, and 48 paraffin-embedded antrum and body biopsies taken from the files of our Department were studied by flow-cytometry. The following markers and parameters were considered: S-phase, proliferation index, PCNA and ploidy. RESULTS: No correlation was found between Hp+ or Hp- gastritis and gastric cell proliferation and no cases of aneuploidy were observed. Gastric proliferation was found to vary depending on the methods, markers and type of biopsy employed. Furthermore, proliferation expressed by PCNA was significantly different in antrum and body. CONCLUSIONS: The commonly studied proliferation markers do not allow the early detection of patients at risk of gastric cancer by flow cytometry. Proliferation differences between body and antrum must be taken into account in the investigation of gastric diseases.

[Pseudolymphoma of the breast involving the periareolar area]. / Pseudolinfoma della mammella a sede periareolare.

Pseudolymphomas are a group of lymphoproliferative disorders which are difficult to classify and diagnose. They can affect several anatomical sites and, among these, a mammary localisation is considered rather rare. Pseudolymphomas of the breast carry an excellent prognosis, and no case of malignant degeneration has ever been described. On the contrary, cutaneous pseudolymphomas, which are considered very low-grade lymphomas by some authors, are actually able to progress to overt cutaneous lymphomas in a minority of cases. The authors present three cases of periareolar pseudolymphoma of the breast. The first two were characterised by the presence of an elevated serum antibody titer to Borrelia, and were therefore diagnosed as lymphocytoma cutis, a disorder affecting 0.6-1.3% of patients with Lyme's disease. Both cases had a benign clinical course, as confirmed by the negative follow-up after more than three years. On the contrary, the third pseudolymphoma, classifiable as an idiopathic form, relapsed locally after ten years, thus testifying to the benign nature of the lesion, but also demonstrating that the lymphoproliferative process may still be active after a long period of time. The last case emphasizes the need for long-term follow-up of these patients.

[Odontogenic myxoma recurring after 11 years: case report and observations on this unusual neoplasm]. / Mixoma odontogeno recidivato dopo 11 anni. Descrizione del caso clinico e considerazioni su una neoplasia rara.

Odontogenic myxoma is usually a benign neoplasm, although it has the ability to infiltrate surrounding tissues thus becoming locally invasive. Furthermore, it has a moderately high recurrence rate and can sometimes display a really aggressive behaviour. An unusual case of a 48-y-old woman in whom odontogenic myxoma recurred 11 years after excision of the primitive lesion is reported. Although rare, the possibility of malignant evolution led us to consider which was the most appropriate management of both the neoplasm and the recurrence. A careful assessment of the clinical, radiographical, tomographical, histological and, if necessary, immunohistochemical features of the lesion allows a distinction to be made between lesions that are only locally invasive and the rarer, more dangerous aggressive lesions. In the first case we suggest that, where possible, a conservative treatment should be preferred, followed by close monitoring of the lesion over time. Since odontogenic myxoma is limited to the facial bones, excision may be uselessly disfiguring, above all in young patients. More aggressive surgical treatment should be reserved for lesions for which there is a strong suspicion of malignant transformation.

Associated localization of morphea and lichen planus of the lip in a patient with vitiligo.

Morphea, lichen planus and vitiligo are common diseases, but seldom associated. Morphea or lichen planus in the lips have not frequently been reported, and an associated localization of both lesions in the lip mucosa is indeed a rare event. A case of morphea and lichen planus localized in the upper lip mucosa in a patient with vitiligo is reported. Immunohistochemistry revealed a clear prevalence of T-lymphocytes in the inflammatory infiltrates of morphea and in the band-like infiltrate of the lichen, a finding consistent with previous reports of morphea, lichen planus, and vitiligo. The inverse ratio found between CD8+ and CD4+ lymphocytes, compared to other reports, seems to confirm that the pathogenesis of morphea and lichen planus evolves through different stages. The present report, besides presenting a rare case, may prompt to consider a common pathogenesis among morphea, lichen planus and vitiligo.

Potential advantages of using synchrotron X-ray based techniques in pediatric research.

Synchrotron radiation (SR), which combines extremely high intensity, high collimation, tunability, and continuous energy spectrum, allows the development of advanced X-ray based techniques that are becoming a uniquely useful tool in life science research, along providing exciting opportunities in biomedical imaging and radiotherapy. This review summarize emerging techniques and their potential to greatly enhance the exploration of dynamical biological process occurring across various spatial and temporal regimes, from whole body physiology, down to the location of individual chemical species within single cells. In recent years pediatric research and clinic practice have started to profit from these new opportunities, particularly by extending the diagnostic and therapeutic capabilities of these X-ray based techniques. In diagnosis, technical advances in DEI and KES imaging modalities have been demonstrated as particularly valuable for children and women since SR allows dose minimization, with significant reductions compared to conventional approaches. However, the greatest expectations are in the field of SR based radiotherapy, increasingly studies are demonstrating SR radiotherapy provides improved chances of recovery; this is especially the case for pediatric patients. In addition, we report on the applicability of advanced X-ray microscopy techniques that offer exceptional spatial and quantitative resolution in elemental detection. These techniques, which are useful for in vitro studies, will be particularly advantageous where investigators seek deeper understanding of diseases where mismetabolism of metals, either physiological important (i.e. Cu, Zn) or outright toxic (i.e. Pb), underlies pathogenesis.

Metastasis of high grade renal cell carcinoma, clear cell type, in fibrous dysplasia with superimposed giant cell reparative granuloma.

A case of monostotic fibrous dysplasia in a 54-year-old male complaining of severe pain in the right hip is presented. Imaging findings demonstrated an extremely aggressive lesion involving bones, liver, lungs, and lymph nodes, and suggested the possibility of sarcomatous transformation. Histological examination established a diagnosis of metastatic high-grade renal carcinoma, clear cell type, and demonstrated the presence of superimposed giant cell reparative granuloma. This latter is a rare example of giant cell reparative granuloma arising in a long bone and in association with fibrous dysplasia. The clinical, radiographic, and histopathologic features of fibrous dysplasia and giant cell reparative granuloma are discussed.

[The Pathology museum of Trieste. From medical arachaeology to revitalization]. / Il Museo "Patologico" di Trieste. Dall'archeologia sanitaria alla rivitalizzazione?

Abandoned in the attic of Trieste's Ospedale Maggiore--which since 1872 housed the hospital's Department of Pathological Anatomy, then known as the Prosettura--is a "museum" of pathology that comprises a heterogeneous collection of anatomic specimens: traumatic, inflammatory and neoplastic lesions, as well as specimens of tattooed skin and hymens. All this material, most of which dates back to the end of the nineteenth and to the start of the twentieth century, will soon be recovered and displayed in a museum. Because this operation has given rise to an interesting discussion on the very significance--both present and past--of this kind of museum, we believe it necessary to extend the debate to those in charge of similar collections and to all our colleagues in the medical profession. It is our opinion that this operation may be justified and meaningful, provided that each specimen is presented with adequate reference to its historical and scientific context.

Carl von Rokitansky and the Italian translation of the Handbuch der Pathologischen Anatomie: a linguistic and doctrinal enigma.

Carl von Rokitansky was the author of a treatise that came out between 1842 and 1846 with the title Handbuch der Pathologischen Anatomie. A historical milestone in pathological anatomy, Rokitansky's work represented the first attempt to systematically classify pathological specimens. Its publication inevitably made a great impact on Vienna, at that time the major European medical centre. The Italian translation of Rokitansky's masterpiece, Trattato Completo di Anatomia Patologica, published in Venice in 1852, was carried out by Ricchetti and Fano: the former a philologist and the latter a Triestine physician who, in 1873, had worked at Simon Pertot's side, the first prosector to be assumed in Trieste. From the start, the two translators not only made no secret of the linguistic obstacles they came up against, but also how unconvincing Rokitansky's doctrines were; a scepticism emerged from their words that inevitably contributed to the realization of a translation difficult to read. Undoubtedly, Rokitansky elaborated a theory of disease containing a certain degree of unclarity and in this respect it is interesting to emphasize that even the English translation, Manual of Pathologic Anatomy (1849-1854), demonstrated similar conceptual problems. A convinced supporter of gross pathology, Rokitansky put forth a theory of disease, the so-called Krasenlehre, resting upon humoral doctrines. This new knowledge inevitably exerted a great influence over Viennese, as well as German, medicine. Rokitansky's humoral pathology survived until the 1850s, when it was attacked by young Virchow, the future, universally recognized, father of cellular pathology, who definitively extinguished speculative humoral pathology.

Cytomorphological variations, proliferation and angiogenesis in the prognosis of cutaneous melanoma.

Depth of invasion and stage of the disease are well known prognostic indicators in cutaneous melanoma (CM). However, the role of other parameters, such as the variations in cytomorphology of melanocyte tumours, mitotic activity and angiogenesis is still open to question. The aim of this study was to analyse proliferation by mitotic activity index (MAI) and immunostaining of proliferating cell nuclear antigen (PCNA), and the intensity of neovascularization (microvessel density; MVD) in CM clinical stage I in relation to epithelioid, spindle and nevoid cell type, histological type (superficial spreading melanoma and nodular melanoma), Clark's level and Breslow thickness. Finally, the role of all parameters in the prognosis of CM was evaluated. Statistical analysis demonstrated that cytological characteristics of CM correlate only with Clark's level, while histological types correlate with MAI, PCNA and MVD. MAI and PCNA also showed correlation between groups according to Clark's level and Breslow thickness. Finally, tumour cell PCNA was found to correlate with MVD. Survival of patients with CM correlated significantly with MAI. These results suggest that cytological variation, histological type, PCNA and MVD alone are not independent prognostic parameters, whereas MAI is a potentially important prognostic marker in CM.