Multiple primary malignancies and subtle mucocutaneous lesions associated with a novel PTEN gene mutation in a patient with Cowden syndrome: case report.

BACKGROUND: Cowden syndrome (CS) is a cancer predisposition syndrome associated with increased risk of breast, thyroid, and endometrial cancers, and is characterized by development of benign mucocutaneous lesions. CASE PRESENTATION: Here we report on a 58-year-old woman with multiple primary malignancies and subtle mucocutaneous lesions such as small polyps and wart-like papulas. Over a period of 23 years, she developed various malignant neoplasms including thyroid, ovarian, stomach, and colon carcinomas, and a benign meningioma. Direct sequencing analysis of the PTEN gene revealed a novel germline mutation (c.438delT, p.Leu146X). CONCLUSION: This case demonstrates that Cowden syndrome is a multi-system disease that can result in the development of multiple malignant and benign tumors.

Comparison of morphological, immunohistochemical, and molecular genetic features of inflammatory fibroid polyps (Vanek's tumors).

Vanek's tumor (inflammatory fibroid polyp) is a rare benign lesion occurring throughout the digestive tract. Histologically, two patterns can be recognized. Classical Vanek's tumor contains concentric formations of proliferating spindle cells which are CD34 positive. Atypical, inflammatory pseudotumor-like Vanek's tumor lacks concentric formations and is CD34 negative. Recently, mutations in platelet-derived growth factor receptor alpha (PDGFRA) were reported in gastric and small intestinal Vanek's tumors. In this study, KIT exons 9, 11, 13, and 17, PDGFRA exons 12, 14, and 18, and a part of exon 15 BRAF for point mutation V600E were screened in 23 cases of Vanek's tumor, both classical (n = 16) and inflammatory pseudotumor-like (n = 7). No mutations in all analyzed exons of KIT and BRAF and in exon 14 of PDGFRA were detected. Six Vanek's tumors harbored activating mutations in PDGFRA exons 12 (n = 5) and 18 (n = 1) respectively: S566_E571delinsK (n = 1), S566_E571delinsR (n = 4), and D842 del (n = 1). The mutations were detected in the classical (n = 5), as well as inflammatory pseudotumor-like (n = 1) Vanek's tumors. The results of this study suggest that the two morphological patterns of Vanek's tumor more probably represent only variants of one type of tumor than two different lesions. Furthermore, BRAF mutations were not shown to drive growth of PDGFRA wild-type Vanek's tumors.

Renal cell carcinoma metastatic to the pancreas: a single center experience.

BACKGROUND/AIMS: Metastatic renal cell carcinoma (RCC) is a malignant tumor characterized by great variation in the clinical course and unusual sites of metastases. Metastases to the pancreas are, in general, rare. METHODOLOGY: A retrospective chart review of patients treated a single institution. RESULTS: Single center experience in 10 patients with this rare presentation of metastatic RCC is presented. In most cases, the course after diagnosis of RCC pancreas metastases was relatively favorable, specifically in patients treated with surgical removal of the metastases. The median survival from the diagnosis of RCC pancreas metastases was 56 months. CONCLUSIONS: The course of disease in patients with RCC pancreas metastases is often indolent. Long-term survival may be obtained after surgery even with suboptimal systemic therapy. An active therapeutic approach is warranted in these patients.

Expression of p53, p21 and p16 does not correlate with response to preoperative chemoradiation in gastric carcinoma.

BACKGROUND/AIMS: A retrospective evaluation was oerformed to determine whether the intensity of p53, p21 or p16 expression predicts response to preoperative chemoradiotherapy in locally advanced gastric carcinoma. METHODOLOGY: Thirty-six patients (cT2-4 or N+) were studied. Preoperative treatment consisted of 30-45Gy of radiation with continuous 5-fluorouracil and weekly cisplatin. Expression of p53, p21 and p16 in pretreatment biopsies was assessed by immunohistochemistry. Level of expression was determined from the intensity and extent of staining. Tumor downstaging was defined as a reduction of at least one T-stage level and/or finding of intense tumor regression in histopathologic examination. RESULTS: Seventeen patients responded to chemoradiation: 8 patients had pathologic complete response, 9 patients were downstaged. The multivariate analysis showed no significant influence of p53 (p = 0.76), p21 (p = 0.10) nor p16 (p = 0.70) expression upon tumor response. Response was found in 52% of patients with low, and in 40% of patients with high p53 staining (p = 0.21); in 54% of patients with low, and in 30% of patients with high p21 staining (p = 0.14); and in 48% of patients with low, and in 43% of patients with high p16 staining (p = 0.32). CONCLUSIONS: We found no significant influence of p53, p21 nor p16 expression upon response to preoperative chemoradiotherapy in gastric carcinoma.

Epidermal growth factor receptor as a predictor of tumor response to preoperative chemoradiation in locally advanced gastric carcinoma.

PURPOSE: The purpose of our study was a retrospective evaluation whether the intensity of epidermal growth factor receptor (EGFR) expression predicts tumor response to preoperative chemoradiotherapy in patients with locally advanced gastric carcinoma. PATIENTS AND METHODS: Thirty-six patients with gastric adenocarcinoma (cT2-4 or N+) were studied. Preoperative treatment consisted of 30-45 Gy of gastric irradiation with continuous 5-fluorouracil and weekly cisplatin. Surgical resection was performed 4-6 weeks later. EGFR expression in pretreatment tumor biopsies was assessed by immunohistochemistry. Level of EGFR expression was determined from the intensity and extent of staining. Tumor response was defined as a reduction of at least one T-stage level and/or finding of intense tumor regression in histopathologic examination. RESULTS: Seventeen patients responded to preoperative chemoradiation -- 8 patients (22%) had pathologic complete response, 9 patients (25%) were downstaged. Positive EGFR expression was found in 8 tumors (22%), and represented a significant predictive marker of poor tumor response in multivariate logistic regression analysis (p = 0.015). Response to chemoradiotherapy was found in 60% (16/28) of EGFR negative patients and in 13% (1/8) of EGFR positive patients (p = 0.044). None of the eight EGFR positive patients achieved pathologic complete response in comparison with 8/28 (29%) of patients with EGFR negative staining (p = 0.16). CONCLUSION: EGFR may represent a molecular marker predictive for poor response to preoperative chemoradiotherapy in locally advanced gastric carcinoma.