Prognostic significance of MGMT gene promoter methylation in differently treated metastatic melanomas.

AIMS: The methylation status of the MGMT gene promoter, considered of prognostic significance by enhancing chemosensitivity to alkylating drugs in gliomas and melanomas, was evaluated in a series of primary melanomas and metastases of patients treated with different therapies, to identify any correlation with the patients' outcome or response to different therapeutic regimens. METHODS: Twenty-nine primary melanomas and 74 metastases, collected from 52 patients, were assessed for MGMT gene promoter methylation using a standard methylation specific PCR-based method. All materials were formalin fixed and paraffin embedded. RESULTS: One of 29 primary melanomas (3.4%) and 22 of 74 metastases (29.7%) showed MGMT gene promoter methylation. MGMT methylation was more frequent in visceral (17/40, 42.5%) than in cutaneous/lymph node metastases (5/34, 14.7%) (p = 0.019). Both disease free (DFS) and overall survival (OS) were significantly longer in patients with methylated metastases (p = 0.009 and p = 0.007, respectively). No correlations were found among methylation, therapeutic regimens and DFS or OS. CONCLUSIONS: MGMT methylation appears to be a late event in the biological history of melanoma and is more frequently seen in visceral metastases. The MGMT gene promoter methylation in metastatic disease is associated with longer survival, irrespective of therapy. Thus it could be considered a prognostic factor in metastatic melanoma.

Well-differentiated papillary mesothelioma of the epididymis in a man with recurrent haematospermia.

We present a case of well-differentiated papillary mesothelioma of the epididymis occurring in a 60-year-old man who came to urologic consult after recurrent episodes of haematospermia. The patient denied pain, fever and trauma in genitals. Local examination revealed indolent swelling at the right testicle and ecography localised a well-circumscribed nodule at the epididymis tail, measuring 2 cm in greater diameter, with associated haemorrhagic hydrocele. A nodulectomy was performed and the patient is alive with no evidence of disease 17 months following surgery.

Activating c-KIT mutations in a subset of thymic carcinoma and response to different c-KIT inhibitors.

BACKGROUND: To analyze a multi-institutional series of type C thymic carcinomas (TCs) (including neuroendocrine tumors), focusing on the expression and mutations of c-KIT. MATERIALS AND METHODS: Immunohistochemical expression of c-KIT/CD117, p63, CD5 and neuroendocrine markers, as well as mutational analysis of c-KIT exons 9, 11, 13, 14, 17 by direct sequencing of 48 cases of TCs. Immunohistochemical and molecular data were statistically crossed with clinicopathological features. RESULTS: Overall, 29 tumors (60%) expressed CD117, 69% were positive for CD5 and 85% (41 cases) for p63. Neuroendocrine markers stained all six atypical carcinoids and five poorly-differentiated thymic squamous cell carcinomas. Overall, six CD117-positive cases (12.5%) showed c-KIT mutation. No mutation was detected in CD117-negative tumors and carcinoids. All the mutations were found in poorly-differentiated thymic squamous cell carcinomas expressing CD117, CD5, p63 and lacking neuroendocrine markers (6 of 12 cases with these features). Mutations involved exon 11 (four cases: V559A, L576P, Y553N, W557R), exon 9 (E490K) and exon 17 (D820E). CONCLUSIONS: All TCs need an immunohistochemical screening with CD117, while c-KIT mutation analysis is mandatory only in CD117-positive cases, particularly when coexpressing CD5 and p63, lacking neuroendocrine differentiation. The finding of c-KIT mutation can predict efficacy with different c-KIT inhibitors.

Rapidly-growing hemangioma of the testicle clinically simulating an aggressive neoplasm. A case report.

We present a case of intraparenchymatous capillary-type hemangioma of the testicle in an adult. The patient was a 37-year-old man who showed a rapidly enlarging and palpable mass in left testicle. Radical orchiectomy was performed, and histological examination revealed an unencapsulated lobulated tumour with wide hemorrhagic portions. To our knowledge, the occurrence of rapid enlargement in a testicular hemangioma has not been previously reported, which might be explained by the development of intra-tumoural haemorrhage.

Expression of estrogen receptor in hemangioma of the uterine cervix: reports of three cases and review of the literature.

The occurrence of hemangioma in the female genital tract, particularly in uterine cervix, is rare. The majority of them show asymptomatic behavior. Surgical excision remains curative in most of the cases. Conservative therapies such as sclerosing agents, cryotherapy, and CO(2) laser excision may be alternatively applied. We present three cases of hemangiomas of the cervix in asymptomatic women, diagnosed as cavernous hemangioma in two cases and capillary hemangioma in one. All tumors were immunoreactive for CD31, CD34, factor-VIII-related antigen. Focal expression of estrogen receptors was detected. No positivity was obtained with progesterone receptor antibodies. The presence of estrogen receptor in the endothelial cells of the hemangioma of the cervix suggests a direct role of this hormone in the hemangioma development. A possible target therapy is discussed.

Giant genital cavernous haemangioma: case description and surgical management.

Giant genital haemangiomas are rare occurrences. Once properly diagnosed, they should be managed by surgery with wide and deep margins. We present a clinical case and provide suggestions for diagnosis and treatment of this unusual pathology.

The value of c-kit mutational analysis in a cytokeratin positive gastrointestinal stromal tumour.

The expression of cytokeratins in gastrointestinal stromal tumours (GISTs) is rare and may lead to diagnostic confusion when it occurs. This report describes a metastatic GIST that stained strongly for cytokeratins, CD117, and CD34 in a patient who was previously diagnosed with gastric epithelioid angiosarcoma. A review of both tumours showed the same histological and immunohistochemical profiles, and c-kit molecular analysis revealed an insertional mutation at codon 558 of exon 11 in both tumours. Thus, pathologists should be aware that GISTs can occasionally express cytokeratins, and that c-kit mutational investigations may have a key diagnostic role and may prevent diagnostic mistakes that could have important clinical implications.