Genetic profiling using plasma-derived cell-free DNA in therapy-naïve hepatocellular carcinoma patients: a pilot study.

Background: Hepatocellular carcinomas (HCCs) are not routinely biopsied, resulting in a lack of tumor materials for molecular profiling. Here we sought to determine whether plasma-derived cell-free DNA (cfDNA) captures the genetic alterations of HCC in patients who have not undergone systemic therapy. Patients and methods: Frozen biopsies from the primary tumor and plasma were synchronously collected from 30 prospectively recruited, systemic treatment-naïve HCC patients. Deep sequencing of the DNA from the biopsies, plasma-derived cfDNA and matched germline was carried out using a panel targeting 46 coding and non-coding genes frequently altered in HCCs. Results: In 26/30 patients, at least one somatic mutation was detected in biopsy and/or cfDNA. Somatic mutations in HCC-associated genes were present in the cfDNA of 63% (19/30) of the patients and could be detected 'de novo' without prior knowledge of the mutations present in the biopsy in 27% (8/30) of the patients. Mutational load and the variant allele fraction of the mutations detected in the cfDNA positively correlated with tumor size and Edmondson grade. Crucially, among the seven patients in whom the largest tumor was ≥5 cm or was associated with metastasis, at least one mutation was detected 'de novo' in the cfDNA of 86% (6/7) of the cases. In these patients, cfDNA and tumor DNA captured 87% (80/92) and 95% (87/92) of the mutations, suggesting that cfDNA and tumor DNA captured similar proportions of somatic mutations. Conclusion: In patients with high disease burden, the use of cfDNA for genetic profiling when biopsy is unavailable may be feasible. Our results support further investigations into the clinical utility of cfDNA in a larger cohort of patients.

[Splenic hamartoma]. / Amartoma splenico.

The Authors present a case of Splenic Hamartoma. This is a rare unique complex vascular lesion of the spleen. This is also a recently reinterpreted lesion with some persistent confusion regarding its definition, histogenesis and classification. The patient is a young woman who following a check up with a raised erythrocyte sedimentation rate underwent abdominal sonography demonstrating an incidental slightly hypoechoic nodular splenic lesion. The pathologic study of the splenectomy specimen showed a large (10 cm) sharply demarcated mass. Histologically the lesion presented a remarkably angiomatoid lobular-nodular configuration with abundant fibrosclerotic stroma with areas of calcification. The immunohistochemical study revealed within the angiomatoid tissue different types of blood vessels: a) capillaries CD31+, CD34+, CD8-; b) structures consistent with splenic venous sinuses CD31+, CD34+/- , CD8-/+; c) small veins CD31+, CD34+, CD8-. The Authors judge this complex picture as indicative of a Splenic Hamartoma with a peculiar lobular-nodular pattern that seems to coincide with the recently described SANT: Sclerosing Angiomatoid Nodular Transformation of the spleen. In this report the Authors discuss the pathology of the lesion and the problems concerning its vasular profile. It is also emphasized the Hamartoma's great variety of morphologic patterns derived from the preponderant growth of one or another of several histologic components. This is the cause of the presence in literature of some different pathologic entities which today are fairly recognized as part of a large pathologic spectrum of the same lesion. The Authors discuss the differential diagnosis of Splenic Hamartoma with other lesions as haemangiomas and inflammatory pseudotumor.

[Hypertrophic and polypoid gastropathy associated with juvenile adenomatous polyposis coli]. / Gastropatia ipertrofica e polipoide associata a poliposi del colon di tipo giovanile ed adenomatoso.

Juvenile Polyposis is a syndrome with gastrointestinal polyps and increased cancer risk. The commonest form of this syndrome is inherited as autosomal dominant trait and presents as Familial Juvenile Polyposis Coli. Another variant involves mainly the stomach and another is generalized throughout the gastrointestinal tract. We present the case of two brothers with polyposis coli complicated by colonic cancer. The polyps were of juvenile, adenomatous and mixed types. The two patients after a decade of colonic endoscopic polypectomies presented gastric involvement by polyps and needed multiple endoscopic gastric resections. One brother underwent total gastrectomy. This stomach showed diffuse polyposis of hyperplastic and fundic gland types within an unexpected background of foveolar and glandular hypertrophic gastropathy. The patients at present are followed up with endoscopic procedures.

[Lupus glomerulonephritis. Study of 21 cases: clinico-morphological correlations]. / Glomerulonefrite lupica. Studio di 21 casi: correlazioni clinico-morfologiche.

The authors report their experience, based on 21 cases, on lupus glomerulonephritis with clinic-morphological correlation and follow-up. They classified renal biopsies utilizing WHO classification and applying a numerical score system proposed by Austin. This system considers the morphological characters referable to duration (chronicity index: C.I.) and activity (activity index: A.I.) of renal disease. Histological data have been connected with clinical evolution of renal disease. Patients have been followed for periods varying from 8 months to 8 years. From data obtained we can see that there is not a constant relation between a high chronicity index or activity index and unfavorable evolution of disease. Besides the authors report a revision of literature considering the possibility of connection between morphological data and the prognosis of lupus glomerulonephritis. They refer contrasting judgements about this.

Reactive glioma in intracranial sarcoma ('sarcoglioma'). Histology, electron microscopy and immunohistochemistry of two additional cases.

The clinicopathologic features of 2 cases of sarcoglioma are described. This rare type of mixed brain tumor is composed of a central core of sarcoma with peripheral distribution of gliomatous elements with gradual transition from reactive to neoplastic astrocytes. The immunohistochemical features showed a strict positivity to glial fibrillary acidic protein only in glial cells, a positivity to vimentin prevalently in sarcomatous cells, whereas the factor VIII-related antigen was negative in astrocytes as well as in sarcomatous cells. The different origin of two neoplastic components is demonstrated well by an ultrastructural study. The morphological observations together with an adequate clinical setting contribute to separate this specific entity from other mixed brain tumors.