Aragona F

Xanthogranulomatous Cholecystitis: Histopathological Study and Classification

Xanthogranulomatous cholecystitis (XC) is a chronic inflammatory lesion of the gallbladder histologically characterized by the presence of varying amounts of foamy histiocytes in the inflammatory infiltrate. In this study a review of 63 cases selected from 1207 surgically removed gallbladder is presented; the percentage found (5.2%) is slightly higher than that of previous reports showing that XC is less uncommon than generally believed. A detailed microscopic study is performed: the authors observed according to the histological features particularly the different patterns of distribution of the inflammatory infiltrate and postulate the existence of three subtypes of XC: multinodular, focal and diffuse XC. Finally, the main etiopathogenetic hypotheses are briefly discussed.

Biological aggressiveness evaluation in prostate carcinomas: immunohistochemical analysis of PCNA and p53 in a series of Gleason 6 (3+3) adenocarcinomas

We selected 63 prostate tumors with Gleasons grade 6 (3+3), commonly showing both tubular and cribrous patterns. We compared in both patterns the expression of two of the most used biologic markers: PCNA and p53, with the aim to verify the validity of the Gleasons grading system to compare the morphologic grade with biologic aggressiveness and prognostic value. We did not find any statistical difference in the protein immunopositivity, indicating that both patterns could have identical biologic behaviour; then we confirmed the validity of Gleasons system for considering both tubular and cribrous patterns as an intermediate grade of tumoral differentiation. Moreover, we found a linear relationship between the increase of PCNA and the accumulation of mutated p53; this datum could confirm the hypothesis that p53 mutation is a late event in prostate carcinogenesis.

‘Pyogenic granuloma‐like Kaposi's sarcoma’ on the hands: immunohistochemistry and human herpesvirus‐8 detection

© 2008 The Authors JEADV 2009, 23, 570–620 Journal compilation

Hypoxia inducible factor-1 alpha expression is increased in infected positive HPV16 DNA oral squamous cell carcinoma and positively associated with HPV16 E7 oncoprotein

BackgroundThere is increasing evidence for the role of High Risk (HR) Human PapillomaVirus (HPV) in the pathogenesis of Oral Squamous Cell Carcinoma (OSCC). The E6 and E7 oncogenes from HR HPVs are responsible for the deregulation of p53 and pRB proteins involved in cell cycle and apoptotic pathways. In cell lines experiments, the HPV E7 protein seems to be able to enhance Hypoxia Inducible Factor-1 alpha (HIF-1α) activity, normally involved in the response to hypoxia and able to enhance angiogenesis.ResultsWe studied tumor specimens from 62 OSCC; a higher prevalence of tumors in TNM stage II and also in pT2 class between OSCC infected positive HPV16 DNA than non-infected ones was observed. HIF-1α positivity was detected throughout the analysed fields, not associated with areas of necrosis and also observed in cells immediately adjacent to blood vessels. A significant increase in mean values of the HIF-1α labeling indexes was observed for pT1-T2, as well for stage I-II, in the infected positive HPV16 DNA tumors than non-infected ones. HIF-1α and HPV16 E7 labeling indexes showed a significantly positive correlation which suggested a positive association between HPV16 E7 and HIF-1α expression.ConclusionsIn our specimens HIF-1α immunoreactivity hints for an O2-independent regulatory mechanism in infected positive HPV16 DNA tumors, especially for pT1-T2 and stage I-II tumors, suggesting a very early involvement in the development of HPV-induced OSCC. HIF-1α and HPV16 E7 labeling indexes suggest also a positive association between the two proteins in infected positive HPV16 DNA OSCC.

Morphometric study of the bone marrow in polycythemia vera following interferon-alpha therapy.

Bone marrow cellularity and extent of fibrotic change were determined in nineteen patients with polycythemia vera, treated with interferon-alpha (IFN) for 1 year. The cellularity was evaluated with an interactive semiautomatic method using Leitz TAS plus microscope: in particular, number and size of megakaryocytes were evaluated after immunostaining with Y2/51 (CD 61); reticulin content was studied by light microscope with a semiquantitative method. Before IFN therapy mean cellularity was 80.5% (+/- 13.7). After 6 and 12 months mean cellularity was 75.4% and 68.4% respectively. Six months after cessation of IFN therapy the cellularity was 69.1%. A decrease of the number, density and morphometrical parameters of megakaryocytes was also remarked. Reticulin fibrosis was mild in 13 cases and moderate in 6 cases before IFN therapy. Reticulin content was unmodified during therapy in all cases but two, in which fibrosis changed from mild to moderate. In conclusion IFN therapy is to be considered a good method in polycythemia vera for the control of proliferative activity of bone marrow but with IFN therapy one cannot determine regression of marrow fibrosis.

Glut-1 expression and in situ CD1a/CD57 immunologic deficit in keratoacanthoma and squamous cell carcinoma of immunocompetent patients.

It is not easy to reach a differential diagnosis between keratoacanthoma (KA) and squamous cell carcinoma (SCC) and furthermore there is still considerable discussion about the relationship of these 2 tumors with immunity. To facilitate such a diagnosis, we assessed the Glut-1 antibody, reported to be strongly and diffusely expressed in SCC but never assessed in KA. We studied 43 lesions of immunocompetent patients: 17 SCCs, 13 typical KAs (tKAs), and 13 atypical KAs (aKAs), with histologic features of SCC in less than 30% of the lesions. In tKA, Glut-1 stained only the basal layers of the squamous nests (basal pattern) whereas in SCC the squamous nests were randomly and diffusely stained (diffuse pattern). In aKA, a biphasic pattern was observed, with the typical KA areas showing the basal pattern and the SCC-like areas showing the diffuse pattern. Glut-1, therefore, helps to distinguish tKAs from SCCs and highlights the intermediate aKA group, supporting the hypothesis of a progression from KA to SCC. Finally, we used CD1a, CD57, CD4, CD8, CD3, and CD20 antibodies to assess whether or not the progression might be related to an in situ immunologic deficit. Significant differences were found both in CD1a+ cells, more numerous in tKA than in SCC and in CD57+ cells, more numerous in tKA than in aKA and in SCC. This suggests a local immunological failure in aKA and SCC, probably related to the action of UV rays, leading us to consider KA as a model for the study of the interaction of skin cancer and immunity.

Predictive role of histological features and Ki67 pattern on high-risk HPV presence in atypical cervical lesions.

the Laboratory of HealthCare Associated Infection, Specialist and Reference Microbiology Division, Colindale, UK, demonstrated S. aureus positive for the PVL gene. Molecular studies by polymerase chain reaction on the postmortem tissue were negative for all influenza, Para influenza, respiratory syncytial and adeno-viruses. Antemortem serological tests for Legionella, mycoplasma, Q fever and psittacosis were also negative. It was concluded that this was haemorrhagic necrotizing pneumonia occurring in a young immunocompetent patient due to S. aureus strain carrying the PVL gene. This was regarded as ‘community acquired’ in our case, as the patient already had established features of pneumonia and septicaemia on admission. Epidemiological evidence so far also suggests that this PVL strain of MRSA is community acquired in most circumstances. As the patient was not immunocompromised, her neutropenia appeared to be the effect of the leukocytotoxic PVL toxin as well as secondary to septicaemia and DIC. Staphylococcus aureus is responsible for about 2% of cases of community-acquired pneumonia and at least 10% of cases of nosocomial pneumonia. Staphylococcus aureus carrying the PVL gene strain is responsible for the community-acquired pneumonias. CA-MRSA has several distinguishing features from hospital acquired (HA)-MRSA, including: presence of the SCCmec IV element and the presence of a gene encoding the PVL toxin; they are more virulent, although relatively sensitive to antibiotics. Depending on multi-locus sequence typing and pulsed-field gel electrophoresis, Vandenesch et al. and Charlebois et al. have concluded that the genetic substance of CA-MRSA and HA-MRSA is diverse and distinct, indicating that CA-MRSA are true strains originating from the community. Therefore, PVL-MRSA ⁄ CAMRSA seems to be a specific disease entity with a poor prognosis. This poor prognosis is probably related to the PVL toxin, which is an extracellular product with a leucocytotoxic action. The prevalence of CA-MRSA is not known, but it can be distinguished from the nosocomial strains clinically by its susceptibility profile (Ciprofloxacin susceptible, fusidic acid resistant). The pathological findings in this case are similar to the (limited) pathology findings described in the literature. The gross appearance of the lungs is similar to either viral pneumonia or adult respiratory distress syndrome, and is different from suppurative pneumonia due to other bacterial infections. Histological features are also distinctly different from other forms of staphylococcal pneumonia with no evidence of suppuration. They more resemble viral pneumonia, except, of course, for the lack of viral inclusions and the presence of large colonies of Gram-positive cocci. Although PVL gene-carrying MRSA pneumonia ⁄ CA-MRSA pneumonia has been reported and recognized in the literature, it is not widely recognized by histopathologists and the detailed pathology of lungs has not been well described. This has important implications. CA-MRSA is likely to present as an acute fulminating illness in previously healthy immunocompetent young adults, culminating in death (within a short period of time). As histopathologists are likely to be performing autopsies in such cases, lack of knowledge of the existence (and pathology) of CA-MRSA ⁄ PVL-MRSA could result in an erroneous diagnosis and cause of death.

CD10 and HHF35 actin in the differential diagnosis between Collagenous spherulosis and adenoid-cystic carcinoma of the breast.

Collagenous Spherulosis (CS) and Adenoid-Cystic Carcinoma (AdCC) of the breast consist of cribriform proliferations of epithelial and myoepithelial cells with an immunophenotypic overlap of some myoepithelial markers, such as p63 and smooth muscle actin (SMA). To our knowledge, CD10 and HHF35 actin have not been assessed in the differential diagnosis of these two breast lesions. We performed an immunohistochemical study on 6 cases of CS and 9 cases of AdCC. We found CD10, muscle-specific actin (HHF35), Estrogen and Progesterone receptors (ER and PR) to be strongly expressed in CS, but not in AdCC; C-kit was diffusely positive in AdCC and scanty in CS; SMA, p63 and Cytokeratine 5/6 (CK5/6) were positive in both. Our results also confirm that AdCC could be true basal-like neoplasia, probably arising from a basal stem line tending to divergent differentiation toward CK5/6/C-kit+, ER/PR-, epithelial basal-like cell type, and toward a myoepitelial-like cell type, with an incomplete SMA/p63+, CD10/HHF35- immunophenotype. By contrast, CS is a reactive, benign proliferation of two well-differentiated cell types: epithelial (ER/PR+, C-kit-) and myoepithelial cells with a complete immunophenotype including CD10/HHF35 positivity. Our study highlights the usefulness of CD10 and HHF35 in the differential diagnosis and helps to understand the histogenesis of the two lesions.

Concomitant Small Cell Neuroendocrine Carcinoma of Gallbladder and Breast Cancer

The neuroendocrine carcinoma is defined as a high-grade malignant neuroendocrine neoplasm arising from enterochromaffin cells, usually disposed in the mucosa of gastric and respiratory tracts. The localization in the gallbladder is rare. Knowledge of these gallbladder tumors is limited and based on isolated case reports. We describe a case of an incidental finding of small cell neuroendocrine carcinoma of the gallbladder, observed after cholecystectomy for cholelithiasis, in a 55-year-old female, who already underwent quadrantectomy and sentinel lymph-node biopsy for breast cancer. The patient underwent radiotherapy for breast cancer and six cycles of chemotherapy with cisplatin and etoposide. Eighteen months after surgery, the patient was free from disease. Small cell neuroendocrine carcinoma of the gallbladder has poor prognosis. Because of the rarity of the reported cases, specific prognostic factors have not been identified. The coexistence of small cell neuroendocrine carcinoma of the gallbladder with another malignancy has been reported only once. The contemporary presence of the two neoplasms could reflect that bioactive agents secreted by carcinoid can promote phenotypic changes in susceptible cells and induce neoplastic transformation.

Relationship between thymidylate synthase and p53 and response to FEC versus taxane adjuvant chemotherapy for breast carcinoma.

Abstract Many drugs can be used for adjuvant therapy of breast cancer, including anthracyclines, cyclophosphamide, 5-fluorouracil (5-FU) and, recently, taxanes (TXT)have shown promising results. 5-FU blocks thymidylate synthase (TS) which cross-links p53 mRNA, inhibiting its synthesis. TS overexpression is one of the main mechanisms involved in 5-FU drug resistance. Enough p53 mutations can confer resistance to chemotherapy using anthracyclines and 5-FU, while are associated with improved responses to TXT. The aim of this study was to examine the TS and p53 levels in tumor samples and to compare the efficacy of FEC (5-FU, epirubicin, cyclophosphamide) and TXT chemotherapy in a group of patients with differing TS and p53 status. We examined 84 breast tumor samples using immunohistochemistry. TS and p53 levels were inversely related, and TS and p53 positivity was significantly associated with the failure of FEC treatment and with a good response to TXT therapy (p <0.001). This confirms the predictive role of these two markers, which should be considered when choosing the appropriate adjuvant therapy for breast cancer.