Data on somatic heterogeneity and germline-somatic interaction in multiple primary melanoma (MPM) patients are limited. We investigated the mutational status of BRAF, NRAS, and TERT promoter genes in 97 melanomas of 44 MPM patients and compared molecular and immunohistochemical findings. We further evaluated the association of somatic alterations with the germline MC1R genotype. Mutations in BRAF gene were identified in 41.2% (40/97) of melanomas, in NRAS in 2.1% (2/97), and in TERT promoter in 19.6% (19/97). Distribution of BRAF mutations did not differ across multiple melanomas (P = 0.85), whereas TERT promoter changes decreased from first to subsequent melanomas (P = 0.04). Intrapatient discrepancy of BRAF mutations among multiple tumors was detected in 14 of 44 MPM patients (32%) and of BRAF/NRAS/TERT promoter genes in 20 of 44 (45%). We observed a high rate of agreement between allele-specific TaqMan assay and immunohistochemistry in BRAF detection (κ = 0.83, P < 0.01) with 86 of 97 melanomas (88.7%) presenting similar BRAF status. Germline MC1R variants were identified in 81.4% (35/43) of MPM patients with no association of MC1R genotype with somatic mutations or with intrapatient concordance of somatic mutational profile. Our results support the genetic diversity of multiple melanomas and show that somatic heterogeneity is not influenced by inherited MC1R variants. Immunohistochemistry may be useful as an initial screening test.

Congenital epulis (CE) of the newborn is an uncommon lesion, described for the first time in 1871 by Neumann.1 To date, fewer than 200 cases have been described in the literature. 2 This lesion, which usually presents at birth, is multiple in 10% of the cases, 3 has a distinct predilection for females, 4 and is most frequently located on the anterior maxillary alveolar ridge. We report a case of CE observed in a newborn male, with immunohistochemical investigation, in order to provide additional information about the histogenesis of this lesion. Case ReportThe patient was a newborn male, 4100 g in weight, 51 cm in length (Crown-Heel), who presented at birth with a pedunculated neoformation on the anterior maxillary ridge, measuring 10x5x5 mm in size. The lesion was excised at four days of age. The excised mass, which consisted of a pink nodule, was fixed in 10% buffered formalin. The specimen was embedded in paraffin to obtain 4-μm thick sections, and stained with hematoxylin and eosin. Further dewaxed sections were taken for immunohistochemical investigation, using the streptavidin-biotin-alkaline phosphatase method. New fuchsin was used as chromogen. The following antibodies were employed: alphafetoprotein (clone C3, Novocastra Lab., Newcastle-upon-Tyne, UK); carcino-embryonic antigen (CEA) (clone Col-1, Biomeda, Foster City, CA); macrophage marker (clone MAC 387, YLEM, Avezzano, AQ, Italy); lysozyme (polyclonal, Novocastra); CD-68 (clone KP1, Biomeda); NSE (clone 5E2, Biomeda); desmin (clone 33, Biomeda); S-100 protein (clone MIG-5, Biomeda); vimentin (clone V9, Biomeda); muscle-specific actin (clone HHF-35, Biomeda); leukocyte common antigen (clone X16/99, Novocastra); estrogen receptors (clone 1D5, DAKO SpA, Milano, Italy); and progesterone receptors (clone 1A6, DAKO). Positive and negative controls were performed in parallel for all the antibodies tested, and all antibodies were prediluted.Microscopic examination showed a highly vascularized tissue, mainly composed of nests of polygonal cells, with large clear and granular cytoplasm and a small nucleus. The overlying mucosa showed normal squamous epithelium with focal ulcerations. Also present were infiltrates of polymorphonuclear leukocytes within the neoformation (Figures 1 and 2).The results of the immunohistochemical investigation were graded as negative (-), weakly positive (+), moderately positive (++) or strongly positive (+++), and are summarized in Table 1. A sharp positivity was observed only for vimentin, whereas desmin appeared focally and moderately positive. All other antibodies were negative. Six years after surgical excision, the patient was well and no local recurrence had been observed.

Histological activity has the most powerful prognostic value in predicting the need for steroids in patients with UC in stable clinical remission on mesalazine. It could be considered as a target of therapy in UC.

In literature there are few reports about multiple CGCG. But this is the first report of bilateral CGCG of the mandibular angles in three females from the same family.This report describes three cases of females from the same family - a mother and two young daughters - with bilateral CGCG in their jaw angles. All the lesions were surgically removed and the histopathologic diagnosis was always identical: giant cell central granulomas, with patterns that were absolutely superimposable between them and with that of the mother.The hypothesis is that this presentation of CGCG may be defined as hereditary bilateral CGCG of the mandibular angles (or also, cherubism-like lesions).

The association between inflammatory bowel disease (IBD) and colorectal cancer (CRC) is being increasingly investigated. HtrA1 overexpression inhibits cell growth and proliferation by influencing apoptosis, invasiveness and migration of tumour cells. In the present study, HtrA1 expression was analysed in 228 colon tissue samples from patients with CRC, adenoma with high-grade dysplasia (AHD), adenoma with low-grade dysplasia (ALD), ulcerative colitis of >10 year duration (UCL), ulcerative colitis of <5 year duration (UCS) and colonic diverticulitis (D), and was compared with its expression in normal colon tissues (NCTs) collected 5 cm from the CRC lesion and in healthy colon mucosa (HC), to establish whether HtrA1 can serve as a biomarker for these conditions. All tissue specimens came from Italian Caucasian subjects. The main finding of the present study was that HtrA1 expression was significantly reduced in CRC and UCL tissues compared with that observed in both NCT and HC samples and with tissues from the other patients. In particular, a similar HtrA1 expression was detected in the stromal compartment of UCL and CRC samples. In contrast, the HtrA1 level was significantly lower (p=0.0008) in UCL compared with UCS tissues, suggesting an inverse relationship between HtrA1 expression and ulcerative colitis duration. HtrA1 immunostaining in the stromal compartment of AHD and ALD tissues showed no differences compared with the HC tissues. No data are available on the immunohistochemical localization of HtrA1 in CRC or IBD. The present findings suggest that HtrA1 could serve as a marker to identify UCL patients at high risk of developing CRC.