Evidence suggests that metastatic colorectal carcinoma (mCRC) has a high level of intratumor heterogeneity. We carried out a quantitative assessment of tumor heterogeneity for KRAS, NRAS, BRAF and ...PIK3CA mutations, in order to assess potential clinical implications.
Tumor samples (n = 182) from the CAPRI-GOIM trial of first-line cetuximab + FOLFIRI in KRAS exon-2 wild-type mCRC patients were assessed by next-generation sequencing that allows quantitative assessment of mutant genes. Mutant allelic frequency was normalized for the neoplastic cell content and, assuming that somatic mutations usually affect one allele, the Heterogeneity Score (HS) was calculated by multiplying by 2 the frequency of mutant alleles in neoplastic cells. Therefore, HS virtually corresponds to the fraction of neoplastic cells carrying a specific mutation.
The KRAS HS ranged between 12 and 260 with mean value of 87.1 and median value of 84.4, suggesting that in most CRC, the majority of neoplastic cells carry mutant KRAS. Similar findings were observed for NRAS (HS range 35.5–146.7; mean 102.8; median 117.1). In contrast, in BRAF (HS range 17.1–120; mean 54.8; median 54.3) and PIK3CA (HS range 14.3–120; mean 59.5; median 47.3) mutant cases, only a fraction of neoplastic cells seem to carry the mutant allele. The response rate was 70% in KRAS mutant patients with an HS <33 (low KRAS; n = 10) and 45.7% in KRAS HS >33 patients (high KRAS; n = 35); median progression-free survival were 7.97 and 8.37 months, respectively. Low-KRAS tumors had a higher frequency of additional mutations in PIK3CA when compared with high-KRAS (6/10 versus 8/35).
KRAS and NRAS mutations are usually present in the majority of neoplastic cells, whereas BRAF and PIK3CA mutations often affect a limited fraction of transformed cells. Resistance to cetuximab in low-KRAS patients might be driven by the complex mutational profile rather than KRAS mutation load.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Serous cystadenocarcinoma of the pancreas is a rare entity. We report on a primary tumor of the pancreas in a 74-year-old male. Computerized tomography showed an abdominal mass within pancreatic ...head, portal vein infiltration and absence of metastatic lesions. Patient underwent Whipple's procedure and portal vein thrombectomy. Pathologic examinations of the specimen showed it to be serous cystadenocarcinoma. To the knowledge of the authors, serous cystic neoplasms of the pancreas have been uniformly benign in biologic behaviour. However, serous cystadenocarcinoma of the pancreas has been reported as a new entity. The current report is the fi rst among 22 cases described to present portal vein thrombosis and might support the local malignant behaviour of this controversial class of tumours.
We describe the case of a 44-yr-old woman, who 2 yr after thyroidectomy for a multinodular goiter with a follicular adenoma showed a rapidly growing mass of the neck causing dysphagia and moderate ...pain. Fine needle aspiration biopsy revealed the presence of fibroblast-like cells, partially with atypical features and no colloid: the cytological diagnosis was suspicious for an indeterminate (mesenchymal) neoplasm. Histological diagnosis, after extensive surgery, indicated aggressive fibromatosis. Immunohistochemistry was positive for vimentin and negative for thyroglobulin. After surgery, nuclear magnetic resonance showed a persistent mass of approximately 2 cm; dysphagia and pain persisted. Therefore, the patient received external radiation therapy (total dose 60 Gy) with clinical benefit. The patient is without symptoms 1 yr after surgery.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
6.
Diabetic mastopathy: A case report GIUNTA, A; VIGNERI, R; MANUSIA, M ...
Journal of endocrinological investigation,
07/2003, Volume:
26, Issue:
7
Journal Article
Peer reviewed
Diabetic mastopathy, although reported since 1984, is a poorly recognized diabetes complication. It more frequently affects pre-menopausal women with Type 1 diabetes mellitus and microvascular ...complications. The pathogenesis of this condition is believed to involve mammary tissue autoimmune reaction to the accumulation of abnormal matrix proteins, caused by hyperglycemia. The lesion often simulates breast cancer; its recognition, therefore, is important to avoid unnecessary diagnostic procedures and surgical treatments. We now report a case of diabetic mastopathy which clinically simulated breast cancer in a young pre-menopausal diabetic woman who, after sonography and mammography, was suggested surgery under suspicion of breast cancer. Histopathological examination by core-biopsy ruled out malignancy.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
About one-third of the cases of non-Hodgkin's lymphomas occur in patients aged 60 years or more. Nevertheless, there are very few data in the literature regarding the optimal therapeutic approach for ...both aggressive and indolent histologies. Fludarabine-based combination regimens are an effective choice for younger patients affected by low-grade non-Hodgkin's lymphomas, but there is a lack of information about their tolerability and efficacy in older patients. We performed a phase II study to test the efficacy and safety of the combination of Fludarabine, Mitoxantrone and Dexamethasone (FND) in newly-diagnosed, chemo-naïve elderly patients affected by low-grade non-Hodgkin's lymphomas with unfavorable prognostic factors. From March 1999 to March 2002, 18 patients were enrolled into the study. All the patients were evaluated for toxicity and response. Neutropenia and thrombocytopenia have been registered as the main toxicities. Thirteen (72%) patients experienced a complete response and 4 (22%) a partial response: the overall response rate was 94%. At a median follow-up of 19 months, the median time for progression-free-survival and the median survival time were not reached yet. The 2-years projected progression-free-survival and overall-survival are 52% and 67% respectively. When administered as first-line treatment to a population of elderly patients affected by high-risk, low-grade non-Hodgkin's lymphomas, FND showed a high efficacy and a good toxicity profile. Our data compare favorably to those reported for the same schedule administered both as first- or second-line therapy in younger patients.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We report a rare case of epithelioid leiomyoma of the uterus presenting as a multilocular cystic mass containing clear fluid. The histologic basis of cysts was the diffuse intratumoral cystic ...degeneration. Histologically, the presence of numerous cystic cavities of variable size raised the possibility that vascular abnormalities, such as hemangioma, lymphangioma, and diffuse cavernous angiomatosis, could be associated with epithelioid leiomyoma. An immunohistochemical study using endothelial cell and basement membrane markers, was helpful in excluding the vascular nature of the cystic cavities and revealed an unexpected focal lymphangioma-like pattern as a peculiar component of tumor.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPUK
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