The role of lung biopsy for diagnosis and prognosis of interstitial lung disease in systemic sclerosis: a systematic literature review.

BACKGROUND: The prognostic and theragnostic role of histopathological subsets in systemic sclerosis interstitial lung disease (SSc-ILD) have been largely neglected due to the paucity of treatment options and the risks associated with surgical lung biopsy. The novel drugs for the treatment of ILDs and the availability of transbronchial cryobiopsy provide a new clinical scenario making lung biopsy more feasible and a pivotal guide for treatment. The aim of our study was to investigate the usefulness of lung biopsy in SSc ILD with a systematic literature review (SLR). METHODS: PubMed, Embase and Cochrane databases were searched up to June 30, 2023. Search terms included both database-specific controlled vocabulary terms and free-text terms relating to lung biopsy and SSc-ILD diagnostic and prognosis. The SLR was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Studies were selected according to the PEO (population, exposure, and outcomes) framework and Quality assessment of diagnostic accuracy studies (QUADAS) were reported. RESULTS: We selected 14 articles (comprising 364 SSc-ILD patients). The paucity and heterogeneity of the studies prevented a systematic analysis. Diffuse cutaneous SSc was present in 30-100% of cases. Female predominance was observed in all studies (ranging from 64 to 100%). Mean age ranged from 42 to 64 years. Mean FVC was 73.98 (+/-17.3), mean DLCO was 59.49 (+/-16.1). Anti-Scl70 antibodies positivity was detected in 33% of cases (range: 0-69.6). All patients underwent surgical lung biopsies, and multiple lobes were biopsied in a minority of studies (4/14). Poor HRCT-pathologic correlation was reported with HRCT-NSIP showing histopathologic UIP in up to 1/3 of cases. Limited data suggest that SSc-UIP patients may have a worse prognosis and response to immunosuppressive treatment compared to other histopathologic patterns. CONCLUSIONS: The data from this SLR clearly show the paucity and heterogeneity of the studies reporting lung biopsy in SSc ILD. Moreover, they highlight the need for further research to address whether the lung biopsy can be helpful to refine prognostic prediction and guide therapeutic choices.

Hepatocellular carcinoma and preneoplastic lesions of the liver: evaluation of argyrophilic nucleolar organizer regions (AgNORs).

The authors applied a silver colloid technique to identify Argyrophilic Organiser Region (AgNOR) to 8 groups of hepatic lesions: alcoholic hepatitis with dysplasia (3 cases); chronic active hepatitis with dysplasia (4 cases); cirrhosis with dysplasia (5 cases); focal nodular hyperplasia (4 cases) and hepatocellular carcinomas (3 cases of grade I, 3 cases of grade II and 5 cases of grade III of Edmondson). Four cases of non-specific reactive hepatitis were used as control. This work suggests the simplicity and utility of simultaneous application of clumps per cell, AgNORs per clump and total AgNORs counts in the evaluation of neoplastic and preneoplastic lesions of the liver. The results show, in hepatocellular carcinomas, a relationship between the number of clumps, the AgNORs per clump, the total number of AgNORs and the grading of Edmondson. The nodular lesions that can be considered in the differential diagnosis with carcinoma are sufficiently well discriminated using the two parameters AgNORs per clump and total number of AgNORs.

Investigation of the patterns of argyrophilic nucleolar organiser regions (AgNORs) in primary gastric lymphomas.

Eight cases of primary gastric lymphomas have been investigated by AgNORs method to individualize the patterns of distribution of NORs. Modifying and exemplifying the scheme of Nikicicz and Norback, previously applied to blood smears and bone marrow in patients affected by leukaemia, the authors found 8 principal distribution patterns of AgNORs. Recording the percentage of the single patterns in every case it was possible to individualize two quite homogeneous groups. The authors maintain that in this way, avoiding complex numerical evaluations and statistical analysis, it is possible to easily classify the gastric lymphomas. We suggest that an improvement of the results could be achieved by comparing the immunophenotype of the cellular lymphomatous populations, and the AgNORs pattern with patients survival.

Colorectal carcinoma and its precursors: role of argyrophilic nucleolar organizer regions (AgNORs).

A silver colloid technique to identify Argyrophilic Organizer Region (AgNOR) was applied to 5 hyperplastic polyps, 5 adenomas with low grade dysplasia, 5 adenomas with high grade dysplasia and 15 adenocarcinomas of the large bowel (5 well differentiated, 5 moderately differentiated and 5 poorly differentiated). The authors suggest the plainness and usefulness of simultaneous application of clumps per cell, AgNORs per clump and total AgNORs counts in the evaluation of neoplastic and preneoplastic lesions of the colon. In fact the results show that the number of clumps per cell is useful to distinguish hyperplastic polyps from adenomas with high grade dysplasia and from all the adenocarcinomas. Using the number of AgNORs per clump there is significant difference between hyperplastic polyps and adenomas with high grade dysplasia and between adenomas with low grade dysplasia and well differentiated adenocarcinomas. Finally the total number of AgNORs can discriminate hyperplastic polyps from adenomas with high grade dysplasia and these from adenomas with low grade dysplasia.

Gastric carcinoma: histopathology, immunocytochemistry and variations of nucleolar organizer regions (AgNORs).

The true nature of Nucleolar Organizer Regions Argyrophilic related proteins (AgNORs) is still unknown, but there is wide agreement that their number expresses the nuclear activity. We undertook an investigation on fifty cases of gastric adenocarcinomas (previously grouped morphologically into well and poorly differentiated) applying together with the AgNOR technique, histochemical (Alcian Blue/PAS, High Iron Diamine) and immunohistochemical methods (alpha-1-antitrypsin, alpha-1-antichymotrypsin and lysozyme). AB/PAS was more frequently positive in well-differentiated adenocarcinomas. On the contrary HID was prevailingly positive in poorly differentiated adenocarcinomas. alpha 1 ACT was expressed in all poorly differentiated adenocarcinomas and in a few well-differentiated adenocarcinomas, whereas lysozyme and alpha 1 AT were never expressed. The AgNORs were more numerous, larger, clumped and irregular in shape in poorly differentiated adenocarcinomas. Considering that alpha 1 ACT reactivity seems to be well correlated with survival and given that there is a good correlation between the aforementioned characteristics of AgNORs and the expression of alpha 1 ACT, our investigation suggests that the four techniques used in this study could be useful to predict the prognosis.

Is adipose tissue a normal component of the myocardium?

We performed a histological comparative study between endomyocardial biopsies taken from 138 patients with various cardiac pathologies and from 42 autoptic hearts (all negative for right ventricular dysplasia), measuring the amount of adipose tissue in isolation or associated with fibrous tissue. In the clinical cases these features were present in 24 instances on the right and in one on the left side of the ventricular septum, to an extent of more than 20% of the section in six patients, clinically positive for right ventricular dysplasia. On autoptic biopsy, fibro-adipose tissue was found in seven hearts, with different distribution on both ventricles, but to a maximum amount of 20% of the section. The right side of the ventricular septum was affected in five instances. Therefore in our material there is a quantitative difference on right ventricular biopsy with respect to fibro-adipose tissue in normal hearts and in cases with right ventricular dysplasia.