PET/CT imaging detects intestinal inflammation in a mouse model of doxorubicin-induced mucositis.

Introduction: A severe side effect of cancer chemotherapy is the development of gastrointestinal mucositis, characterised by mucosal inflammation. We investigated if 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography combined with computed tomography (2-[18F]FDG-PET/CT) could visualise gastrointestinal mucositis in mice treated with the chemotherapeutic agent doxorubicin. Methods: In this study, gastrointestinal inflammation was longitudinally evaluated by 2-[18F]FDG-PET/CT scans before and 1, 3, 6, and 10 days after treatment with doxorubicin. Doxorubicin-treated mice were compared to saline-treated littermates using the abdominal standard uptake value of 2-[18F]FDG corrected for body weight (SUVBW). Results: Abdominal SUVBW was significantly increased on day 1 (p < 0.0001), day 3 (p < 0.0001), and day 6 (p < 0.05) in the doxorubicin-treated group compared to controls. Abdominal SUVBW returned to baseline levels on day 10. In the doxorubicin group, the largest weight loss was observed on day 3 (control vs doxorubicin, mean percent of baseline weight: (98.5 ± 3.2% vs 87.9 ± 4.6%, p < 0.0001). Moreover, in the doxorubicin-treated group, villus lengths were decreased by 23-28% on days 1 and 3 in the small intestine (p < 0.05), and jejunal levels of tumour necrosis factor and interleukin-1ß were significantly increased on day 3 (p < 0.05). Discussion: Together, these findings indicate that sequential 2-[18F]FDG-PET/CT scans can objectively quantify and evaluate the development and resolution of intestinal inflammation over time in a mouse model of doxorubicin-induced mucositis.

[Asymptomatic amoebiasis colitis detected during colonoscopy].

In this case report, a tumour was found in the coecum under a colonoscopy, performed after positive screening test for colorectal cancer in an asymptomatic 61-year-old man. Pathology from biopsies showed numerous trophozoites in the lamina propria, compatible with Entamoeba histolytica. In faecal samples, E. histolytica was detected by species-specific real-time polymerase chain reaction. Infection caused by E. histolytica can occur several years after exposure. If E. histolytica is detected, treatment is always recommended as prevention for later development of invasive infection.

Synchronous detection of pancreatic adenocarcinoma and paraganglioma in a Whipple resection specimen.

We report a case of a pancreatic ductal adenocarcinoma (PDAC) presenting synchronously with a paraganglioma (PGL) in a Whipple reaction specimen. The patient was a 72-year-old female with a history of breast and vulvar cancer. The simultaneous occurrence of two synchronous tumours in the pancreas was striking. Due to the presence of PGL and multiple meta- and synchronous tumours, the patient was referred to genetic counselling. Tumour tissue from the vulvar carcinoma, the PDAC and the PGL was analysed by targeted next-generation sequencing (NGS) of 161 cancer-related genes and by whole exome sequencing (WES). Peripheral blood was also examined by NGS and WES. These genetic analyses revealed germline polymorphisms in AXIN2 (NM_004655.4:c 0.2272 G>A; p.Ala758Thr), BRCA2 (NM_000059.3:c.9976 A>T; p.Lys3326Ter), NCOR1 (NM_006311.4:c 0.6544 G>A; p.Ala2182Thr) and SPTA1 (NM_003126.3:c 0.373 G>A; p.Ala125Thr) and somatic mutations of KRAS (NM_033360.3;c 0.35 G>A; p.Gly12Asp) and TP53 (NM_000546.5; c.602delT; p.Leu201CysfsTer46) in the PDAC and of TP53 (NM_000546.5; c 0.733 G>A; p.Gly245Ser) and TERT (NM_198253.2; c.-124 C>T; promotor region) in the vulvar carcinoma. Breast carcinoma tissue was not available for genetic analysis. The results of the genetic analyses did not explain the presence of multiple tumours in this patient, despite a slightly increased risk of breast cancer associated with the identified BRCA2 polymorphism. To our knowledge, this is the first report of the synchronous occurrence of PDAC and PGL. This case emphasizes the importance of thorough macroscopic examination of pancreatic resection specimens, as coexisting neoplasms may otherwise be missed.

Subtyping of male breast cancer by PAM50 and immunohistochemistry: a pilot study of a consecutive Danish cohort.

Male breast cancer (MBC) is a rare disease that is still to be fully understood. In female breast cancer, molecular subtyping by gene expression has proven its significance. In this study, we characterize a consecutive cohort of MBC patients surgically treated from 1997 to 2017, identified at our institution (N = 37), and report the association between molecular subtypes found by a surrogate panel of immunohistochemical (IHC) markers, and the PAM50 signature, as well as risk of recurrence score and overall survival for the different subtypes. PAM50 subtypes were determined using the nCounter FLEX system instrument and software. The distribution of molecular subtypes according to the PAM50 signature was as follows: 56% luminal B, 39% luminal A, and 5% basal-like. None of the tumors were HER2-enriched. Using IHC surrogate markers, we found 80% luminal B-like, 15% luminal A-like, and 5% basal-like. None were HER2-positive (non-luminal). We found a strong statistical association between subtypes found by PAM50 signature and the IHC surrogate markers (p < 0.001). Furthermore, we found luminal A tumors to be smaller in size compared to luminal B tumors (p = 0.04). Patients with luminal A subtype tumors had the lowest ROR scores with a mean of 39, whereas patients with luminal B subtype tumors had a mean ROR score of 69. Significant worse overall survival for luminal B tumors compared to luminal A tumors was seen (p = 0.02). Male breast cancer seems to be a mainly luminal disease, with luminal B being the most frequent subtype. Further studies are needed to ensure correct therapeutic strategies for this select group of patients.

Tissue variations of mosaic genome-wide paternal uniparental disomy and phenotype of multi-syndromal congenital hyperinsulinism.

Mosaic genome-wide paternal uniparental disomy (GW-pUPD) is a rarely recognised disorder. The phenotypic manifestations of multilocus imprinting defects (MLIDs) remain unclear. We report of an apparently non-syndromic infant with severe congenital hyperinsulinism (CHI) and diffuse pancreatic labelling by 18F*-DOPA-PET/CT leading to near-total pancreatectomy. The histology was atypical with pronounced proliferation of endocrine cells comprising >70% of the pancreatic tissue and a small pancreatoblastoma. Routine genetic analysis for CHI was normal in the blood and resected pancreatic tissue. At two years' age, Beckwith-Wiedemann Syndrome (BWS) stigmata emerged, and at five years a liver tumour with focal nodular hyperplasia and an adrenal tumour were resected. pUPD was detected in 11p15 and next in the entire chromosome 11 with microsatellite markers. Quantitative fluorescent PCR with amplification of chromosome-specific DNA sequences for chromosomes 13, 18, 21 and X indicated GW-pUPD. A next generation sequencing panel with 303 SNPs on 21 chromosomes showed pUPD in both blood and pancreatic tissue. The mosaic distribution of GW-pUPD ranged from 31 to 35% in blood and buccal swap to 74% in the resected pancreas, 80% in a non-tumour liver biopsy, and 100% in the liver focal nodular hyperplasia and adrenal tumour. MLID features included transient conjugated hyperbilirubinaemia and lack of macrosomia from BWS (pUPD6); and behavioural and psychomotor manifestations of Angelman Syndrome (pUPD15) on follow-up. In conclusion, atypical pancreatic histology in apparently non-syndromic severe CHI patients may be the first clue to BWS and multi-syndromal CHI from GW-pUPD. Variations in the degree of mosaicism between tissues explained the phenotype.

Phyllodes tumor with a benign heterologous osseous component: a diagnostic challenge.

Phyllodes tumors (PTs) are rare fibroepithelial neoplasms of the breast and constitute 0.3-1% of all primary breast tumors. They should be characterized in to a benign, borderline or malignant category based on a combination of histological features. PTs can show heterologous components, typically sarcomatous, including osteosarcomatous and chondrosarcomatous. Benign heterologous components are exceedingly rare with only one prior reported case in the English literature. This case emphasizes how difficult establishing a correct diagnosis in PTs with heterologous components can be, especially when the tumor consists mainly of a benign heterologous component. We report the case of a 65 year old woman with a recurrent breast tumor initially misdiagnosed as benign osseous metaplasia. The tumor re-occurred as a malignant PT dominated by benign osseous and chondroid metaplasia. Multiple metastases consisting of primarily mature bone and cartilage were seen in the lungs. On microscopic revision and considering the clinical course the primary breast tumor was re-classified as a borderline PT.