Epidemiological, clinical and pathological characteristics of gastric neoplasms in the province of Cremona: the experience of the first population-based specialized gastric cancer registry in Italy.

BACKGROUND: The gastric cancer incidence rate differs widely across geographical areas. In Italy, in the province of Cremona the incidence is high, compared to the national situation. For this reason a specialized population-based registry was set up. METHODS: The collection encompasses all gastric cancers diagnosed in the three districts of the province since January 1, 2010. The main data sources were the pathological and Hospital Discharge Records and patient clinical charts. Only diagnoses of primary gastric cancer were considered. For each case the following variables were registered: personal data, medical history and symptoms at diagnosis; imaging assessments performed, details on surgery and other treatments received; genetic background and biomolecular characteristics; social and environmental factors. RESULTS: As of November 2017, 1087 cases were collected; of which 876, diagnosed up to December 2015, were analyzed. Male/female ratio was 1.4. The European Age-standardized Incidence Rate was 41.4 for males and 28.3 for females as compared to a national average of 33.3 and 17.0 respectively. Median age at diagnosis was 73 for male and 78 for female. Helicobacter Pylori infection was present in fewer than 20% of cases. HER-2 gene was amplified in about 25% of cases. Primary tumour location was the gastro-esophageal junction or cardia in 17.5% in males and 8.3% in females. The majority of cases (58.3%) were diagnosed at an advanced stage and overall only 41.2% underwent surgery. Median overall survival was 14.8 months for men and 18.5 for women. Age standardized 5-year relative survival was 31.4% for men and 40.5% for females. Neoadjuvant treatment was performed in fewer than 10% of patients who underwent surgery, and the rate of postoperative therapy adherence was low. DISCUSSION: This study shows a high gastric cancer incidence in the province of Cremona, with a geographical spread across different districts. Moreover, a high percentage of gastric cancers were detected at an advanced stage of disease and a low rate of 5-year relative survival was registered. Based on these findings, effective preventive interventional health strategies and screening procedures need to be implemented to reduce the impact of this pathology in this geographical area.

Eosinophilic cytoplasmic inclusions in type 2 papillary renal cell carcinoma.

A case of a patient with type 2 papillary renal cell carcinoma with eosinophilic cytoplasmatic inclusions is presented. About 50% of tumor cells were characterized by a well-circumscribed intra-cytoplasmatic round-to-oval or irregular inclusion/globule. Inclusions were 7-30 micron in diameter. They were glassy and pale to slightly eosinophilic in color in hematoxylin and eosin, were stained red by trichrome and were negative for periodic acid-Schiff reaction. Immunohistochemically, globules were negative for PAX8, epithelial membrane antigen, Carbonic Anhydrase IX, pan-cytokeratin (AE1/AE3), CD10, S100 protein, α-smooth-muscle actin, cytokeratin 7 and cytokeratin 34ßE12. Glassy hyaline globules were not detected in any adjacent normal kidney cells. The presence of eosinophilic cytoplasmic inclusions in renal cell carcinoma, especially in papillary renal cell carcinoma, has been rarely emphasized in the literature. In this article, we review similar cases in the literature and discuss the nature of eosinophilic globules.

Cutaneous infiltration of plasmacytoid dendritic cells and T regulatory cells in skin lesions of polymorphic light eruption.

BACKGROUND: Polymorphic light eruption (PLE) is the most common autoimmune photodermatosis. Plasmacytoid dendritic cells (PDCs) are important mediators of innate antimicrobial immunity involved in the pathogenesis of many inflammatory skin diseases. In addition to PDCs, regulatory T cells (Tregs) are involved in controlling inflammation and adaptive immunity in skin by their immunosuppressive capacity. OBJECTIVE: The aim of this study was to investigate the presence of PDCs and Tregs in photoexposed skin from PLE compared to healthy skin. METHODS: Patients with PLE diagnosis and healthy controls were recruited and underwent a photoprovocative test. A 4-mm punch biopsy was taken from the site of positive photoprovocation test reaction, and immunohistochemistry for BDCA2 as marker for PDCs, CD4 and FOXP3 as markers for Tregs was performed. Double immunostain for FOXP3 and CD4 was performed as well. Absolute counts for CD4, BDCA2 and FOXP3 were performed in at least 5 High Power Fields (HPF). Percentage of CD4-, BDCA2- and CD4FOXP3-positive cells over the total inflammatory infiltrate was assessed for each case. RESULTS: We enrolled 23 patients and controls. BDCA2+ cells were present in 91.3% of PLE skin samples and 100% of healthy volunteer. Both in PLE patients and healthy controls, PDCs distribution was mainly dermic (P < 0.05). Compared to healthy controls, both epidermic and dermic BDCA2+ cells count were significantly higher in PLE patients (P < 0.05). Both in PLE patients and healthy controls, Tregs distribution was mainly dermic (P < 0.05). The presence of both CD4+ cells and FOXP3+ cells was significantly higher in the dermis of PLE patients compared to controls (P < 0.05). Relative percentages of cellular infiltrations confirmed these results. CONCLUSIONS: D-PDCS and Tregs may play a significant role in the development of PLE, and dermal distribution of PDCs in PLE skin biopsies seems to confirm a possible overlap with cutaneous lupus erythematosus (CLE).

Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with T2 to T4, N0 and N1 breast cancer.

BACKGROUND: Histological status of axillary lymph nodes is an important prognostic factor in patients receiving surgery for breast cancer (BC). Sentinel lymph node (SLN) biopsy (B) has rapidly replaced axillary lymph node dissection (ALND), and is now the standard of care for axillary staging in patients with clinically node-negative (N0) operable BC. The aim of this study is to compare pretreatment lymphoscintigraphy with a post primary systemic treatment (PST) scan in order to reduce the false-negative rates for SLNB. METHODS: In this single-institution study we considered 170 consecutive T2-4 N0-1 M0 BC patients treated with anthracycline-based PST. At the time of incisional biopsy, we performed sentinel lymphatic mapping. After PST, all patients repeated lymphoscintigraphy with the same methodology. During definitive surgery we performed further sentinel lymphatic mapping, SLNB and ALND. RESULTS: The SLN was removed in 158/170 patients giving an identification rate of 92.9% (95% confidence interval (CI) = 88.0-96.3%) and a false-negative rate of 14.0% (95% CI = 6.3-25.8%). SLNB revealed a sensitivity of 86.0% (95% CI = 74.2-93.7%), an accuracy of 94.9% (95% CI = 90.3-97.8%) and a negative predictive value of 92.7% (95% CI = 86.1-96.8%). CONCLUSION: Identification rate, sensitivity and accuracy are in accordance with other studies on SLNB after PST, even after clinically negative node conversion following PST. This study confirms that diagnostic biopsy and neoadjuvant chemotherapy maintain breast lymphatic drainage unaltered.

Lymphoid abnormalities in CD40 ligand transgenic mice suggest the need for tight regulation in gene therapy approaches to hyper immunoglobulin M (IgM) syndrome.

Mutations in the CD40 ligand (CD40L) are responsible for human hyper immunoglobulin M (IgM) syndrome. The absence of the interaction between CD40L, expressed by T lymphocytes, and the CD40 receptor present on the surface of B cells is responsible for the inability of B cells to carry out the isotype switch from IgM to the other Ig classes. This leads to a fatal immunodeficiency for which no cure exists. For these reasons, the CD40L gene is a good candidate for gene therapy studies. To investigate the possible effects of the expression of this tightly regulated gene in vivo, we produced transgenic mice in which CD40L expression was deregulated. Widespread ectopic expression appears to be lethal. Overexpression in mature T cells is compatible with life, but in one-third of the cases, mice developed atypical lymphoid proliferations which, occasionally, progressed into frank lymphomas. Even though gene therapy is one of the most promising approaches to cure human hyper IgM syndrome, these results suggest that when we modify very tightly regulated genes such as cytokines or other growth factors, particular care has to be taken to avoid excessive stimulation of the target cells.

[Gastric polypoid angioma: a rare cause of bleeding in the elderly. Report of a case and review of the literature]. / L'angioma polipoide gastrico: una rara causa di sanguinamento nell'anziano. Rapporto su un caso e revisione della letteraura.

In 10,700 upper gastrointestinal endoscopies performed between 1990 and 1995; one case of gastric haemangioma was observed. The rarity of this tumour, which represents 0.05% of all the digestive neoplasms is underlined and its features and clinical history are reported. This case and the other four reported in Italy during the last fifteen years are critically reviewed. The various diagnostic-therapeutic pictures emerging from literature are examined.

[Prognostic factors in organ-confined renal epithelial tumors]. / Fattori prognostici nei tumori renali epiteliali organo-confinati.

Recent application of molecular cytogenetic techniques to the evaluation of epithelial renal cell tumors have showed some characteristic combinations of genetic alterations within the chromosomal DNA. Moreover each group of abnormalities has been correlated with peculiar tumor morphology. The new classification of renal cell neoplasms proposed by G. Kovacs, based on specific genetic alterations, and histologic pattern, together with the morphologic and pathologic features that correlate with survival has been discussed.

Uterine endometrioid adenocarcinoma with extensive pilomatrixoma-like areas. A case report.

Shadow cells are typical features of pilomatrixoma, although they have been described in other benign cutaneous tumours with characteristics of differentiation toward the hair matrix. The finding of extensive shadow cell differentiation in visceral carcinomas is otherwise unusual. We report herein a case of uterine adenocarcinoma with extensive pilomatrixoma-like areas in a 74-year-old woman. The endometrial tumour showed an invasive poorly differentiated growth with squamous differentiation deeply extending into the myometrium intermixed with lobules of empty squamoid polyhedral cells with clear shadow like nuclei, focally exhibiting a 'ghost' appearance. The cervix, salpinges, ovaries and pelvic lymph nodes were free of disease and, taking all evidence into account, the tumour was diagnosed as poorly differentiated endometrial endometrioid adenocarcinoma (FIGO stage IB). The recognition of an extensive pilomatrixoma-like component in a high- grade endometrioid adenocarcinoma may be important to avoid diagnostic misinterpretation with uterine metastases of malignant cutaneous pilomatrical tumours, such as pilomatrix carcinomas.

Desmoplastic melanoma: report of 5 cases.

Background. The clinical presentation of desmoplastic melanoma is often challenging. We report the experience of the Melanoma Unit of Spedali Civili University Hospital of Brescia, Italy. Method. Study subjects were drawn from 1770 patients with histologica confirmed melanoma. Within this group, desmoplastic melanoma developed in 5 patients. For each diagnosed melanoma, histological characteristics, treatment, and outcomes were evaluated. Results. Of the 5 patients described in this study, 2 were males and 3 females. The average age was 62.4 years ranging from 56 to 68 years. Breslow thickness ranged from 2.1 to 12 mm with a mean thickness of 5.8 mm. Primary treatment of 5 patients included a wide local excision of their primary lesions. Conclusions. Desmoplastic melanoma is a rare neoplasm which clinically may mimic other tumours or cutaneous infiltrate of uncertain significance. The diagnosis is hiastopathological and radical resection is necessary.

Fatal hemophagocytic syndrome related to active human herpesvirus-8/Kaposi sarcoma-associated herpesvirus infection in human immunodeficiency virus-negative, non-transplant patients without related malignancies.

Hemophagocytic syndrome (HS) may occur as a consequence of herpes viral infections. Human herpesvirus 8 (HHV-8)/Kaposi sarcoma-associated herpesvirus has so far been recognized as a trigger of HS only in immunosuppressed subjects or in patients with Kaposi sarcoma and/or HHV-8-related lymphoproliferative diseases. We report two Italian human immunodeficiency virus (HIV)-negative elderly men who developed an HS with a rapidly fatal course, following treatment with corticosteroids for autoimmune hemolytic anemia. An overwhelming active infection with HHV-8 was unequivocally documented by molecular and immunohistochemical methods, in the absence of HHV-8-related tumors. The occurrence of HHV-8-associated HS, although rare, may be considered, even out of the HIV or the transplantation settings, at least in areas endemic for HHV-8 infection.

Kaposi's disease and sarcoidosis.

A human immunodeficiency virus (HIV) antibody-negative 65 year old woman was treated with corticosteroids for 7 yrs because of bilateral uveitis. One year after the beginning of corticosteroid treatment, erythematous skin lesions appeared on the legs. Eight years after the diagnosis of uveitis, gastric and bronchial biopsies revealed noncaseating epithelioid cell granulomas, whilst a cutaneous biopsy showed Kaposi's disease. Sarcoidosis-associated alteration of immune regulation and corticosteroid therapy may have promoted the development of disease.

[LAT (linker for activation of T cells): a useful marker for megakaryocyte evaluation on bone marrow biopsies]. / LAT (linker for activation of T cells): un utile marcatore per l'identificazione di megacariociti in biopsie osteomidollari.

Detection of atypical megakaryocytes in bone marrow biopsies, especially in cases of myelodysplastic syndromes (MDS), chronic myeloproliferative disorders (CMPD) and acute leukemias, is facilitated by staining for markers such as Ulex europaeus agglutinin (UEA)-J, CD31, CD61 and von Willebrand factor (VWF), the latter being considered the most sensitive. Recently, LAT (linker for activation of T cells), a molecule involved in T-cell activation and platelet aggregation, was found to be expressed by megakaryocytes and platelets in tissue sections. We compared VWF and LAT immunoreactivity on megakaryocytes in 64 bone marrow biopsies from 12 normal controls (NC), and from patients with MDS (n=18), CMPD (n=21) and acute megakaryocytic leukemia (AML-M7, n=13). Immunostaining was performed on paraffin sections with polyclonal antibodies against VWF and LAT. Immunoreactivity was evaluated by counting positive megakaryocytes in 10 high-power fields, and values were compared using Student's t test for paired data. Both VWF and LAT predominantly stained the cytoplasm of megakaryocytes, although LAT was also recognizable on the cell membrane. In most biopsies, the immunoreactivity of the two antibodies was quite similar. No significant differences were noticed between the mean values of VWF+ and LAT+ megakaryocytes. However, in 22 cases (5 NC; 5 MDS; 6 CMPD; 6 AML-M7), the number of LAT+ megakaryocytes was at least 30% higher than VWF+cells, while in 3 cases opposite findings were found. In 3 AML-M7 cases, anti-LAT antibodies stained numerous megakaryocytes, but anti-VWF staining was practically negative; in another 5 AML-M7 cases, anti-LAT labeling was much stronger than anti-VWF staining. LAT represents a useful immunohistochemical marker for megakaryocytes in normal and pathological conditions. It seems to be expressed by megakaryocytes more than VWF in most cases and, particularly, in conditions associated with poorly differentiated megakaryocytes, such as acute megakaryocytic leukemias. The use of LAT staining should be recommended in association with other megakaryocyte markers in the study of bone marrow biopsies in cases of hematopoietic disorders.

Intrathymic restriction and peripheral expansion of the T-cell repertoire in Omenn syndrome.

Mutations in the human RAG genes that impair, but do not abolish, recombination activity lead to Omenn syndrome, a severe primary immune deficiency that is associated with clinical and pathological features of graft-versus-host disease and oligoclonal expansion of activated, autologous T cells. We have analyzed the mechanisms accounting for peripheral oligoclonality of the T-cell repertoire. Predominance of few T-cell receptor clonotypes (both within TCRAB- and within TCRGD-expressing lymphocytes) is already detectable in the thymus and is further selected for in the periphery, with a different distribution of clonotypes in different tissues. These data indicate that oligoclonality of the T-cell repertoire in Omenn syndrome is due both to intrathymic restriction and to peripheral expansion. Moreover, the RAG genes defect that causes Omenn syndrome directly affects early stages of V(D)J recombination, but does not alter the process of double-strand-break DNA repair, including N and P nucleotide insertion.

Anthracycline-based chemotherapy as primary treatment for intravascular lymphoma.

BACKGROUND: Optimal therapeutic management of intravascular lymphoma (IVL) lacks precise guidelines. PATIENTS AND METHODS: The clinico-pathological features of 38 HIV-negative patients with IVL were reviewed to define efficacy of chemotherapy in these malignancies. Clinical characteristics of 22 patients treated with chemotherapy and of 16 untreated patients were compared in order to understand better the impact and causes of potential patient selection. RESULTS: Median age was 70 years (range 34-90), with a male/female ratio of 0.9; 23 (61%) patients had Eastern Cooperative Oncology Group performance status (ECOG-PS) > 1; 21 (55%) had systemic symptoms. Cutaneous lesions and anemia were significantly more common among patients treated with chemotherapy; central nervous system (CNS) and renal involvement were significantly more common among untreated patients. Chemotherapy was associated with a response rate of 59% and a 3-year overall survival of 33 +/- 11%. Five of six patients with CNS involvement received chemotherapy: four of them died early; only one patient, treated with adriamycin, cyclophosphamide, vincristine, methotrexate, bleomycin and prednisolone (MACOP-B) followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT), was alive at 19 months. High-dose chemotherapy supported by ASCT was indicated at diagnosis in another patient (43 years of age, stage I), who was alive at 71 months, and at relapse after cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) in two patients who died early after transplantation. PS < or = 1, disease limited to the skin, stage I, and use of chemotherapy were independently associated with better outcome. CONCLUSIONS: Anthracycline-based chemotherapy is the standard treatment for IVL. However, survival is disappointing, with a relevant impact of diagnostic delay and lethal complications. More intensive combinations, containing drugs with higher CNS bioavailability, are needed in cases with brain involvement, and the role of high-dose chemotherapy supported by ASCT should be further investigated in younger patients with unfavorable features.