On the question of cognitive limits in diagnostic histopathology.

From a solely morphological point of view, histopathological diagnosis is subject to interpretation variables that may be investigated from an epistemological aspect. On the basis of the most suitable ways of approach, the authors examine some theoretical aspects involved in writing a histopathological report. In particular, the following are considered: problems regarding the perception of shapes, induction, deduction, abduction and some aspects of formal logic connected with the evaluation of immunohistochemical investigations. The main reasons for diagnostic mistakes are underlined, and the opportunity for an awareness of the logical and mental mechanisms involved in the evaluation of morphological data is outlined.

CagA and VacA Helicobacter pylori antibodies in gastric cancer.

BACKGROUND: Infection with different genotypes of virulent Helicobacter pylori strains (cytotoxin-associated gene A [CagA]- and/or vacuolating cytotoxin A [VacA]-positive) can play a role in the development of atrophic gastritis, duodenal ulcer (DU) and gastric cancer (GC). OBJECTIVE: To determine whether patients with GC and H pylori-negative histological staining had previously been infected with H pylori CagA- and/or VacA-positive virulent strains. METHODS: Twenty-three GC patients with a mean (+/- SD) age of 68.14+/-9.8 years who tested H pylori-negative on histological staining took part in the study. Three control groups were included. The first group comprised 19 patients with past H pylori infection and DUs eradicated 10 years earlier, with a mean age of 58+/-18.2 years. H pylori-negative status for this group was determined every year with Giemsa staining, and follow-up testing occured 120+/-32 months (mean +/- SD) after therapy. The subsequent control groups included 20 asymptomatic children, with a mean age of 7+/-4.47 years, and with H pylori-negative fecal tests; the final group contained 30 patients without clinical symptoms of H pylori infection, with a mean age of 68+/-11.6 years, who tested H pylori-negative by histological staining. RESULTS: Prevalence of CagA and VacA seropositivity, respectively was 82.6% and 73.91% in GC patients; 84.2% and 84.2% in H pylori-negative DU patients; 25% and 5% in H pylori-negative children; and 36.6% and 16.6% in the patients without clinical symptoms on histological staining. CagA and VacA antibody positivity was not significantly different between GC patients and patients with DUs that had been eradicated 10 years earlier. Significant positivity was found between the children's group and the H pylori-negative (with past DUs) group (P<0.001). A statistically significant difference was found in age between groups (P<0.03). CONCLUSIONS: Patients with GC, even when H pylori-negative at the time of the present study, may have been infected by H pylori before the onset of the disease, as confirmed by CagA and VacA seropositivity. These data reinforce the hypothesis that H pylori may be a direct carcinogenic agent of GC.

Helicobacter pylori antibodies (CagA and VacA) detection. The link between cancer and infection.

BACKGROUND: Infection with different genotypes of virulent Helicobacter pylori (Hp) strain, CagA and/or VacA positive, can play a role in the development of atrophic gastritis, duodenal ulcer (DU), and gastric carcinomas (GC). This study was undertaken to investigate if patients with GC with Hp negative histological Giemsa staining had a past infection by virulent strains of Hp CagA and/or VacA positive. METHODS: Twenty GC, (average age +/- SD) 68.14+/-9.8 years old, Hp negative to histological take part to the study. Two-control group were included: 19 Hp infected patients with DU eradicated 10 years before, 58+/-18.2 yrs. Hp negative status was determined every year with histology and follow-up after therapy was 120+/-32 months; range 96-144 months. Twenty asymptomatic children, 7+/-4.47 yrs, with Hp negative faecal test. The immunoblot assay was used to detect serum antibodies against CagA and VacA. RESULTS: Prevalence of CagA and VacA seropositivity was 90 and 95% in GC, 84 and 84% in DU Hp negative, 25 and 5% in children Hp negative, respectively. CagA and VacA antibody positivity was not significantly different between GC and patients with DU eradicated 10 years before. A true significant positivity was found against children (''t''-Student test; p<0.0001). Statistical difference was found in age between groups p<0.03. CONCLUSIONS: Patients with GC, although Hp negative at present, could be infected by Hp before the appearance of the disease as confirmed by CagA and VacA seropositivity. These data may reinforce the idea to consider Hp as a direct carcinogenetic agent of GC.

Gastric carcinoma risk index, type III intestinal metaplasia and Helicobacter pylori status on antrum and body biopsies in a prospective general population study.

BACKGROUND: To evaluate the utility of 2 biopsies of antrum and gastric body on routinary endoscopy for the assessment of type III intestinal metaplasia (IM-3) and Helicobacter pylori (Hp) status, 1750 patients (pts) (895 males and 855 females, mean age 60.2) were considered from June 1998 to June 2000. METHODS: Specimens were graded 0 to 3 for atrophy, IM-3 and Hp status. 620 pts treated previously with antibiotics or not eligible for biopsy were excluded from initial 2360 pts. RESULTS: IM-3 (score >0), was found in 118 pts (6.7%), 86 pts (4.9%) only in the antrum. Ten of 355 pts (2.8%) with normal endoscopy findings and 47 of 702 (6.6%) with non erosive endoscopic gastritis resulted IM-3 positive in the antrum. 709 pts (40.5%) were found positive for Hp in antrum or/and corpus. The presence of Hp and IM-3 in the antrum was not correlated (p=0.99; spearman test). A positive correlation (p=0.000) between duodenal ulcer and Hp was found when antral Hp positivity was taken into account. Gastric carcinoma risk index (GCRI) was found in 358 pts (20.4%); in this group 131 pts (36.6%) were Hp positive, 82 pts (23%) have IM-3, 184 pts (51.4%) have atrophy. CONCLUSIONS: The incidence of IM-3 is low (6.7%) in routinary endoscopy. Normal endoscopy does not exclude the presence of IM-3. The biopsy is necessary to discover IM-3 in the antrum in 5.3% of pts with normal or aspecific endoscopic gastritis. Application of the GCRI might be useful to identify a group of patients carrying a higher risk for gastric carcinoma.

Gastric atrophy and intestinal metaplasia changes 8 years after Helicobacter pylori eradication. A blind, randomised study.

BACKGROUND: Chronic atrophic gastritis and intestinal metaplasia are regarded as predisposing factors for gastric cancer associated with Helicobacter pylori infection, and their severity appears to influence gastric cancer risk. Our purpose was to determine the outcome of chronic gastritis after H. pylori eradication in a long-term follow-up. METHODS: Fifty-four consecutive patients with duodenal ulcer and H. pylori infection were enrolled in the study. Endoscopic examination with antral and corporal biopsy was done at baseline and yearly after conventional eradication therapy (omeprazole 40 mg b.i.d., amoxocyllin 1 g b.i.d and clarithromycin 500 mg b.i.d.). Gastritis, atrophy, and metaplasia were graded according to the updated Sydney System. RESULTS: Twenty-four patients were successfully treated; infection persisted in 14 and 16 dropped out (during the first 5 years of follow-up). Inflammation and mean neutrophil activity significantly decreased in patients in whom H. pylori was eradicated. Glandular atrophy improved in 2 and disappeared in 5/17 patients, whereas intestinal metaplasia improved in 3 and disappeared in 2/12. In the patients in whom H. pylori persisted, inflammatory infiltrate, atrophy and intestinal metaplasia had not significantly decreased during follow-up. In contrast, glandular atrophy worsened in 2 and developed in 5/7 patients. Similarly, intestinal metaplasia did not improve when present and developed in 5/13 cases. CONCLUSIONS: In a long-term follow-up, H. pylori eradication does not affect glandular atrophy, but it seems to prevent the development of precancerous lesions such as intestinal metaplasia.

[Auto-transplantation of tooth germs. Discussion and presentation of 3 treated cases]. / Gli autotrapianti di germi dentari. Considerazioni ed esposizione di 3 casi trattati.

The authors examine the theoretical possibilities of human dental transplants: autologous, homologous and heterologous. They, then discuss-with reference to autologous transplants-an autotransplant as an alternative to prosthodontic treatment. This would apply both to traditional prosthodontic treatment and on implants or orthodontic treatment aiming at filling dental gaps. They show both general and local counterindications against this operational method the knowledge of which is necessary for an adequate selection of patients. They stress the determining factors for a successful autotransplant: 1) particular care with the choice of the germ to be transplanted taking into account its morphology and the stage of root development; 2) adequate surgical preparation of the receiving site in relation to the size of the germ to be transplanted; 3) suitable surgical technique entailing a particular care in the manipulation of soft and hard tissues and of the germ and appropriate conditions of sterilization; 4) use of appropriate retention means to ensure stability of the transplanted germ so as to favour cellular proliferation and reduce osteoclastic activity; 5) reduction of occlusal pressure on the transplanted germ. The authors describe for example's sake 3 out of 32 cases treated with the documentation of the achieved long-term success. They also analyse the possible causes of failure of such operational method (careless manipulation of the germ, incorrect surgical technique, removal of the germ in a too early stage of its development, too long exposure of the germ outside the oral cavity, poor oral hygiene, caries, periodontal disease, occlusal trauma.

Long-term histopathologic findings in tooth germs autotransplantation. Analysis of a series.

Tooth germ autotransplantation, a surgical technique based upon extraction of a germ followed by reimplantation in the same individual, is indicated in tooth agenesis or loss as an alternative to traditional methods of treatment. The success of autotransplantation relies on several factors, and clinical studies indicate that results are excellent if correct surgery is carried out. This work offers a morphological contribution to the understanding of post-transplantation changes of the pulp, periodontal ligament and root cementum.

Helicobacter pylori-positive duodenal ulcer: a long-term double-blind randomized study in patients healed with H2-receptor antagonists.

BACKGROUND: The NIH Consensus Conference in 1994 (1) concluded that all patients with peptic ulcer disease should be tested and treated for Helicobacter pylori and that further evaluation was needed for patients in remission. MATERIALS AND METHODS: We evaluated in a double blind randomization 30 patients whose duodenal ulcers had been healed with H2-receptor antagonists and who remained in remission on maintenance therapy. After ulcer healing and the presence of H. pylori had been confirmed, these patients were randomized to receive eradication therapy or placebo and were followed for a mean period of 23 months. RESULTS: Almost all patients receiving placebo had ulcer recurrence, whereas the patients treated with antibiotics demonstrate a low recurrence rate. CONCLUSION: These data suggest, for the first time to our knowledge, the importance of treating with antibiotics duodenal ulcer patients whose disease is in remission.

[Diffuse pulmonary ossification and diabetes mellitus. An association not previously described]. / Ossificazione polmonare diffusa e diabete mellito. Un'associazione non descritta.

Diffuse pulmonary ossification is a relatively rare, well recognized condition, of which a number of reports exist in the literature. While the histologic picture of diffuse pulmonary ossification, with its nodular and dendritic forms, is well know, the pathogenesis is not yet fully clarified; a number of diseases have been claimed to be responsible for, or associated to diffuse pulmonary ossification, but the association with diabetes mellitus is so far undescribed. That's why we report this case, along with the discussion of some pathogenetic hypotheses and differential diagnosis.

Collagenous spherulosis of the breast. Case report.

We report a case of collagenous spherulosis of the breast, a very rare underinvestigated lesion which must not be misinterpreted as a malignant epithelial tumour, such as adenoid cystic or signet-ring cell intraductal carcinoma, on histologic slides. The lesion is typically found in association with benign proliferative breast diseases. Prognosis is excellent.

[Pheochromocytoma and sudden death: a case of hyperacute myocardial ischemia]. / Feocromocitoma e morte improvvisa: un caso di ischemia miocardica iperacuta.

Pheochromocytoma is the most frequent cause of adrenal sudden death, which is the unique sign in 1.5% of cases. After a short review of the literature, we report a case of a 36 years old asymptomatic woman, who died suddenly and unexpectedly while receiving preoperative treatment. Gross examination did not allow to reveal any cause of death. Microscopy revealed signs of acute myocardial ischemia, in the lack of any coronary and catecholaminic heart disease. Azan-Mallory trichromic stain was found to be necessary in revealing myocardial lesions. A plausible death pathway is the following: a single catecholaminic peak might have induced myocardic vessel spasm, which in turn could be responsible for a lethal arrhythmia; the dramatic pressure drop can be the effect of pump failure or of a paradoxical disproportionate beta stimulation.

[A case of anatomo-clinical diagnosis of balloon cell melanoma metastasis]. / Un caso di diagnosi anatomo-clinica di melanoma a cellule balloniformi su metastasi.

The authors present a case of balloon cell melanoma which was not diagnosed on the skin. The diagnosis was later carried out both on matter from pleural effusion and on lymph node metastases. The cytological examination of the fluid obtained from pleural effusion revealed the presence of abundant neoplastic cells belonging probably to a malignant epithelial lung tumor. Despite several diagnostic examinations no evidence of a neoplastic lesion in the lungs was found. Later histology on metastatic axillary lymph nodes revealed a tumor with the features of a balloon cell melanoma. Immunohistochemical stains revealed a strong S-100 positivity. The patient underwent surgical treatment, but died 2 months later. The balloon cell melanoma is a rare variety of melanoma interpreted by several authors as the expression of a degenerative process caused by the immunological defence of the subject, combined with therapy. This hypothesis is supported by the evidence of high survival rates in some cases. So the importance of an early detection of the malignancy must be stressed once again, in order to avoid missing diagnoses on any skin lesion, though appearing benign to the naked eye.

[Histopathologic aspects of gingival hyperplasia caused by cyclosporin]. / Aspetti istopatologici della iperplasia gengivale da ciclosporina.

The paper analyses a series of patients treated with Cyclosporine-A causing varying gingival degrees of hyperplasia and discusses the histopathological aspects.

[Role of direct immunofluorescence in the diagnosis of oral lichen planus]. / Ruolo della immunofluorescenza diretta nella diagnosi del lichen planus orale.

A series of 25 cases with clinical signs indicative of oral lichen planus was examined. Samples stained with haematoxylin-eosin as for traditional histology and others for DIF were taken in each case. The results obtained by both techniques were then compared with the clinical picture. It is concluded that DIF is a valuable diagnostic aid in doubtful cases.

[Keratotic lesions of the oral cavity. Notes on histopathologic differential diagnosis in leukoplakia, lichen planus, lupus erythematosus. Cases investigation]. / Lesioni cheratosiche del cavo orale. Note di diagnosi differenziale istopatologica tra leucoplachia, lichen planus, lupus eritematoso. Indagine casistica.

A series of 24 white mouth lesions variously diagnosed as leukoplakia, lichen planus and discord lupus erythematosus is examined. A number of histological parameters were investigated using samples stained with haematoxylin-eosin and orcein and by Wohlgemulh's test. The 24 cases were also assessed by direct immunofluorescence (DIF) using the standard techniques. The aim of the study was to discover which of the histological and DIF findings were most helpful for diagnosis. The results confirm the view that histological diagnosis is only possible in some cases and that DIF helps to clarify histologically uncertain ones. Even so, clinical examination of the patient remains essential in order to eliminate the uncertainty created by the histological findings. It therefore follows that close collaboration between clinician and pathologist is essential.

[Structural aspects of degenerative disease of the temporomandibular articulation]. / Aspetti strutturali della malattia degenerativa della articolazione temporo-mandibolare.

The authors, after having considered some structural aspects of the temporomandibular joint, examine the histologic features of the degenerative disease (arthrosis, remodelling, deviation in form).