Toscana virus (TOSV) infection is a frequent cause of meningitis in central Italy during summer. The disease generally has a benign course. Rarely, the infection produces a severe disease, with encephalitis and signs of systemic involvement, including lymphadenopathy. Since there is no clinical necessity of performing lymph node biopsy in such cases, the histopathological feature of TOSV-related lymphadenitis is not known. We herein present a case in which lymphadenopathy preceded the onset of meningitis. The excised lymph node showed a non-specific mixed-type lymphoid hyperplasia, with follicular hyperplasia, sinusal expansion and paracortical involvement. We also demonstrated the presence of viral protein and viral RNA in the lymph node tissue.

Langerhans' cell histiocytosis (LCH) is a clonal, histiocytic, proliferative disorder of unknown aetiology originating from Langerhans' cells. Although the clinical presentation and therapeutic approach to the disease in children have been well established, few data are available concerning the disease in adults. Moreover, unique cutaneous involvement by LCH in a woman older than 70 years has been described very rarely. We report here a case of a 75-year-old woman with cutaneous LCH confined to the inframammary fold, and highlight some medical problems regarding the management of a purely cutaneous form of LCH in adults.

BACKGROUND: Papillary carcinoma can arise from ectopic thyroid tissue, but teratoma have not been described. Differentiation into thyroid follicles does not occur in mediastinal teratomas.CASE: A case of tipper mediastinal immature teratoma occurred in an 18-day-old male newborn. The histologic examination revealed the presence of a discontinuous rim of compressed thyroid follicles on the outer aspect of the tumor capsule. This finding is consistent with the origin of the teratoma in ectopic thyroid tissue, and it has not been previously described in the literature. The patient was free of disease after 22 months, in accordance with the benign behavior of immature teratoma in infancy.CONCLUSION: Ectopic thyroid tissue can undergo the same pathologic changes as the thyroid gland, including the rare occurrence of teratoma. (Anal Quant Cytol Histol 2009;31:233-238)

We reviewed the clinico-pathological features of 73 primary cutaneous B-cell lymphomas (PCBCLs), diagnosed in 10 years in Marche region in central Italy, which included 16 marginal zone lymphomas (MZL), 33 follicle centre lymphomas (FCL) and 24 diffuse large B cell lymphomas (DLBCL). We also investigated the presence of Borrelia burgdorferi in tissues by polymerase chain reaction. Differences in age, sex, location site, response to therapy, disease recurrence and 5-year disease-specific survival were observed among the 3 histological groups. Specific DNA sequences of Borrelia burgdorferi were not detected in any of the 73 cases of PCBCL. We conclude that PCBCLs in Marche region behave according to the literature data and do not seem to be associated with Borrelia burgdorferi. Additional investigations should be performed on other possible etiologies, at least in our geographical area.

OBJECTIVE:To increase knowledge on the behavior of gastrointestinal stromal tumors (GISTs) and factors influencing therapy.STUDY DESIGN:The clinicomorphological features of 158 GISTs were analyzed. Survival analysis was performed on the whole series, as well as on a selected group of patients with high risk GIST who did not receive imatinib mesylate. The impact of imatinib mesylate on the prognosis was investigated.RESULTS:Most of the GISTs had a benign behavior. The risk class was a powerful prognostic factor but was unable to predict the outcome in a single case; even patients in the high risk class not receiving imatinib mesylate had a low mortality rate. In this group, it was the mitotic activity that better correlated with prognosis, and a cut point of 10 mitoses per 50 high-power field can be fixed to discriminate cases with favorable or unfavorable outcome. Patients with GISTs presenting as aggressive disease received great benefit from imatinib mesylate therapy.CONCLUSION:Mitotic activity is important in predicting the outcome of patients with high risk GIST who present at diagnosis without dissemination. This finding can have therapeutic implications.

Extranodal marginal zone B-cell lymphomas are considered at the present time as “infection-associated” tumors, because their occurrence has been observed in the background of a chronic antigenic stimulation started by some recognised pathogenic microbial agents, which do not cause the lymphoid transformation by a direct infection of the lymphocytes, but by maintaining the cells with a prolonged antigenic stimulation in a continuous proliferative status and thus increasing the probabilities of a neoplastic transformation. Among them, the Helicobacter pilori is known to be active in the stomach, the Campylobacter jejuni in the ileum, the Chlamydia psittaci in the eye, the Hepatitis C virus in the spleen, whereas in the skin Borrelia burgdorferi, the agent of Lyme's disease, which can present as erithema migrans as well as a lymphocytoma cutis, has been indicated as a potential agent involved in the pathogenesis of B-cell lymphomas. In some instances, the eradication of the Borrelia has been associated with skin lymphoma regression in cases with documented infection. In Italy there is a great variability of incidence of the disease, which is trasmitted by arthropode-bites and few cases have been observed also in our region, the Marche; this region has approximately one and half million of inhabitants. The aim of our study was to analyse by molecular techniques the presence in tissue of Borrelia burgdorferi DNA in 72 cases of primary cutaneous B-cell lymphomas, diagnosed at the Institute of Anatomic Pathology of Polytechnic Marche Region in Ancona from 1990 and 2004. In all the cases the clinical history was retrieved from clinical charts. On the basis of the pathological findings together with a complete phenotypical and clonality analysis, each case was reclassified according to the recent WHO/EORTC scheme, as follows: 16 cases of marginal-zone lymphomas, 33 cases of follicle-center lymphomas, 23 cases of diffuse large B-cell lymphomas, subdivided in “leg-type” (7), and “other” (16). DNA was extracted by paraffin-embedded tissue and amplified as previously reported, together with DNA extracted from colonies of Borrelia burgdorferi as positive control. None of the 72 cases resulted positive. The efficacy of the PCR method was documented by the expected bands obtained with control samples. Based on our results, the role of Borrelia burgdorferi in the pathogenesis of B-cell lymphomas seems to be unlikely in our geographical area, in agreement with a very low incidence of the Lyme's disease. Therefore, also the specific antibiotic therapy do not seem to have a rationale in lymphoma treatment. Our negative results should represent a basis for searching a different combination of immunological, infectious and genetic factors to explain the occurrence of primary B-cell lymphomas, particularly the marginal types, in our region.

This study correlates bone marrow changes after Rituximab (RTX) treatment with the clinical characteristics and outcome of 26 patients with small B-cell lymphomas. The percentage, phenotypic profile and clonality pattern of bone marrow lymphoid infiltrate were analysed before and after RTX treatment. Clinical, histological and molecular responses to RTX were correlated to the clinical outcome of the patients. Sixteen out of twenty-six patients obtained a complete clinical remission (CR). A favourable histology--follicular lymphoma (FL), hairy cell leukaemia (HCL) and marginal zone lymphoma (MZL)--was associated with a higher frequency of clinical CR and histological remission (HR), in comparison with mantle cell lymphoma (MCL), chronic lymphocytic leukaemia (CLL) and lymphoplasmacytic lymphoma (LPL). Two patterns of bone marrow HR were observed: 1) complete lymphoid cell disappearance (9 patients); or 2) nodular/interstitial T-cell infiltration (10 patients). Three histological persistence (HP) patterns were observed: 1) persistence of CD20+ small lymphoid cells in 1 patient with MCL; 2) loss of CD20 antigen expression in 4 patients with CLL; or 3) persistence only of clusters of monotypic plasma cells in 2 patients with LPL. CR and HR were strongly correlated. The percentage of lymphomatous infiltrate after RTX was higher in patients who subsequently died of the disease. Molecular response showed no correlations with the further clinical course in 12 patients achieving a complete clinical remission. In conclusion, bone marrow morphological and immunohistochemical analysis with a restricted panel of antibodies is useful to avoid 42% false positive and 85% false negative interpretations. Persistence of monoclonality after RTX might have a role in evaluating the molecular pattern of CD20-negative clones that can emerge after RTX as a tumoral escape to therapy.

In the skin of 50–75% patients with early mycosis fungoides (MF) a dominant T-cell receptor (TCR) γ gene rearrangement can be detected. An identical T-cell clone is also detectable in the peripheral blood (PB) in 15–40% of these patients, as well as in 39–61% of skin biopsies showing histological remission after therapy. At the present time, it is still unclear if molecular analyses might be helpful to recognize an unfavourable subset of patients less responsive to skin-directed therapy or with a higher risk of disease recurrence. 89 patients (56 men, 33 women) with a median age of 60 years (range, 17–80), with a histologically confirmed diagnosis of early MF, were treated with a combination protocol of PUVA and low dose IFN-α for 14 months and then closely followed up. Only patients with a dominant clone in the affected skin at diagnosis, and in whom peripheral blood samples at diagnosis and a second tissue biopsy at the end of treatment were available, were selected for the present study. Twenty-four patients (10 men, 14 women; median age 62.5 yrs, range 17–77; 6 in stage IA, 15 IB, 3 IIA) met the inclusion criteria. PCR amplification for TCR γ gene was performed on DNA extracted from formalin-fixed and paraffin-embedded skin tissue samples and from frozen PB lymphocytes, as previously reported. Amplification products were visualised by 10% polyacrylamide gel electrophoresis at the same time, on the same gel, thereby allowing precise comparison of the dominant clonal populations. In one patient the identity of T-cell clones in the skin at diagnosis and at the end of therapy was assessed by sequencing analysis. After a mean time of 4 months (range 1–11), all 24 patients responded to the combination therapy, obtaining a clinical complete remission (CCR), even if three of them showed histological persistence of disease. During the follow-up, 11 patients had a disease recurrence (median time 70 months range 27–108). PCR analysis of TCR γ gene in the PB showed a circulating T-cell clone identical to the one detected in the skin in 9 cases (37.5%) at diagnosis. An identical T-cell clone was observed in the skin at the end of therapy in 17 cases (71%). Disease-free survival curves plotted by Kaplan-Meier method showed that patients with or without a peripheral T cell clone did not behave differently, that is, half of them would have experienced a relapse after a similar period of time in any case. The same behaviour was observed in patients showing different molecular responses after therapy. Only in one third of patients a molecular cure for the disease could be obtained by combination IFN-α and PUVA therapy, since a high rate of persistence of monoclonal PCR signals following CR was observed (71% of CR cases with a dominant clone at diagnosis); surprisingly, such a molecular outcome seems not to protect patients from subsequent disease relapses. On the other hand, our data seems to indicate that the combination of a skin-directed therapy like PUVA in addition to the systemic immunoregulatory effects of IFN-α may abolish the negative influence of a circulating clone.

Objectives: Combined high-dose Interferon-alpha and psoralen plus ultraviolet A irradiation (PUVA) have been reported to be effective in the treatment of early mycosis fungoides (MF); however, our study is the first controlled prospective study in the literature exploring the activity and tolerability of the combination with low dosages and evaluating further clinical outcome of early-MF patients. Methods: We carried out a multicentric prospective Phase II clinical study on 89 patients with early-stage IA to IIA MF treated for 14 months with low-dose IFN-alpha 2b (6-18 MU/wk) and PUVA. Treatment success was analysed in terms of freedom from treatment failure. Results and conclusions: Complete remission (CR) was achieved in 84% and an overall response rate in 98% of cases: six-month CR was associated with a non-confluent skin infiltrate at histology (P = 0.044) and 14-month CR with high epidermal CD1a+ dendritic-cell density (P = 0.030). The combination protocol was successfully tolerated and the most common reason of 'failure' was related to relapse and not to toxicity. Sustained remissions were achieved in 20% of patients. High CD8+ lymphoid T-cell density was associated with a lower relapse rate (P = 0.002). We think that our combination therapy can be considered an alternative approach compared with other modalities. Good immunological host surveillance in the skin lesions seems to be an optimal basis for the therapeutic success.

The development of mucosa-associated lymphoid tissue (MALT) lymphoma is a multistage process. 1 This is best understood in gastric MALT lymphoma, the most common form. Typically, low-grade gastric MALT lymphoma arises from mucosal lymphoid tissue that is acquired usually as a reaction to Helicobacter pylori infection. 2, 3 Low-grade MALT lymphoma is initially confined to the gastric mucosa, and its growth depends critically on the contact help of H pylori–specific intratumoral T cells; therefore, it responds favorably to H pylori eradication therapy. 4-6 However, when the lymphoma invades the deep layers of the gastric wall and disseminates to local lymph nodes and distal sites, the tumor loses its dependence on H pylori-specific T cells and is no longer sensitive to H pylori eradication therapy. 7-9 Finally, low-grade gastric MALT lymphoma may transform into a more aggressive diffuse large B-cell lymphoma (DLBCL). 10, 11 Direct12-14 and indirect antigen stimulation4, 5 and several genetic factors, including genetic instability, 15 trisomy 3, 16 p53 mutation/LOH, 17 p16 deletion, 18 t (1; 14)(p22; q32), 19 and t (11; 18)(q21; q21), 20, 21 are implicated in MALT lymphoma development. However, the molecular events underlying the multistep progression of the tumor remain largely unknown. Identification of the genes involved in MALT lymphoma-specific t (1; 14)(p22; q32) 22, 23 and t (11; 18)(q21; q21) 24-26 has provided fresh insights into the pathogenesis of this disease.T (1; 14)(p22; q32) causes overexpression of BCL10, an apoptosis regulatory molecule. 22, 23 In contrast to its expected oncogenic role, wild-type BCL10 has been …

Alveolar soft part sarcoma (ASPS) is a rare tumor typically located in skeletal muscles and muscolofascial planes. Isolated cases of ASPS have been described as arising in the viscera. We report a mesenchymal tumor of the stomach in a 54-year-old Italian woman without evidence of primary neoplasm elsewhere ten years following the initial diagnosis. The histologic, histochemical, immunohistochemical, and electron microscopic findings were all consistent with the diagnosis of ASPS and allowed differentiating it from morphologically similar and more common tumors, such as metastatic renal cell carcinoma and paraganglioma. The patient is alive and well ten years following the initial presentation.

A high incidence of Helicobacter pylori infection has been found in patients with gastric MALT (mucosa-associated lymphoid tissue) B-cell lymphoma. Recent studies have indicated that the aggressive strains of the bacterium containing the CagA gene may have direct effects on tumourigenesis. To investigate the involvement of CagA+ strains in MALT lymphomagenesis, a sensitive polymerase chain reaction (PCR)-based detection assay for the gene was developed. DNA extracts from paraffin sections of 123 H. pylori-related gastric biopsies from Italy were analysed, including 56 cases of chronic gastritis, 37 low-grade, and 30 high-grade MALT lymphomas: 30·3 per cent (17/56) of the gastritis cases, 37·8 per cent (14/37) of the low-grade, and 76·7 per cent (23/30) of the high-grade MALT lymphomas were found to contain the CagA gene. The frequency of CagA+ strain infection was signfiicantly higher (P<0·05) in high-grade than in low-grade MALT lymphoma or gastritis. These results suggest that high-grade gastric MALT lymphoma transformation may be more likely to occur following infection by CagA+ strains of H. pylori. © 1998 John Wiley & Sons, Ltd.

One hundred and fifty colorectal adenomas were investigated in order to detect the presence of K-ras gene mutation. The adenomas were classified according to the severity of the histological lesion (mild, moderate, or severe dysplasia and carcinomatous transformation) and to the degree of aneuploidy. K-ras mutation was found in 30.8% of cases, mostly consisting of a point mutation of codon 12. K-ras mutation was more frequently found in adenomas > 1 cm and in the villous type. No correlation was otherwise demonstrable with the ploidy pattern of the lesion.

In order to point out differences in the biological behaviour between early and advanced gastric carcinoma, their proliferative activity is evaluated on paraffin sections by silver staining ofNOR particles and by immunohistochemical detection of PCNA. AgNOR particles were measured by a Leitz-Texture Analyzing System. The following variables were considered: nuclear area; area, number and percentage area of AgNOR; mean area of each AgNOR particle. The percentage of PCNA-positive nuclei was calculated. The results failed to show any significant difference of EGC compared to AGC. The possibility that differences in biological behaviour, other than the proliferative activity, could exist between EGC and AGC, is discussed.

The morphology of apocrine cells exfoliated in breast cyst fluid (BCF) was studied in 78 BCF samples obtained from 39 premenopausal patients with gross cystic disease who were bearing two simultaneously aspirated cysts. 5778 samples showed cell clusters suitable for computer-assisted cytometry. This was performed on 5820 cells using a Leitz Texture Analysis System (TAS). We measured the surface areas of cytoplasm, nucleus and nucleolus; we also calculated the nuclear/cytoplasmic (N/C), nuclear/nucleolar (N/n) ratios and the nuclear roundness factor (RF). Cysts were divided according to the cationic pattern of BCF: Type 1, K+Na+ > 1.5; Type II, K+Na+ < 0.66. The cytometric analysis was made on 47 samples of Type 1 and 10 samples of Type II. At the light microscope, no difference was apparent between the apocrine cells coming from Type I or Type II cysts. Cytometric measurements showed significant differences for the apocrine cells aspirated from Type I vs. Type II cysts for the mean cytoplasmic area (97.13 ± 24.28 S.D. μ2 vs. 59.66 ± 14.90 S.D. μ2, respectively) and the mean nucleolar area (4.35 ± 0.99 S.D. μ2 vs. 2.75 ± 0.71 S.D. μ2, respectively). Our data do not allow the inference of apocrine changes in the epithelium lining the cysts simply from the cationic pattern of BCF. The significantly wider cytoplasm and nucleoli of the apocrine cells aspirated from Type I cysts could reflect different functional stages of these particular cells.

In 4538 double-contrast examinations of the upper gastrointestinal tract, 8 early gastric cancers (EGCs) were prospectively diagnosed before endoscopy. Four others were false negative cases, but retrospective analysis led to identification of the lesion in 3. The rate of EGC in radiologically diagnosed and verified cancers was found to be 10.6%. Gastric polyp rarely corresponded to EGC, whereas gastric ulcer more frequently corresponded to an EGC. Five of 12 EGCs were multifocal, with 21 satellite foci of carcinoma, of which 3 were probably radiologically identifiable as varioliform erosions. Routine double-contrast study appears valuable for detecting EGC, but the rate of false negative cases indicates that integration of radiologic, endoscopic, and cytologic data as well as accurate histopathologic study of the surgical specimen are needed to diagnose and characterize early gastric carcinoma.