Cardiac Melanoma Metastasis with ERBB2 Gene Amplification: A Potential for Future Targeted Therapy.

Cardiac tumors are rare, and their treatment differs interindividually regarding the histopathological proprieties and the stage of disease. Authors present a case of symptomatic cardiac melanoma metastasis that expressed an ERBB2 (HER2) gene amplification in a course of the disease that has not yet been reported. The frail patient with a history of pulmonary and renal carcinoma, was admitted to the hospital due to a symptomatic left atrial tumor mass. The patient underwent a tumor-resecting cardiac surgery. At first mistaken for myxoma on echocardiography, the histopathological examination of the tumor revealed a melanoma of acral or mucosal origin. The melanoma metastasis was negative for common genetic mutations in BRAF, NRAS or KIT genes, and for the presence of NTRK genes fusions, but carried ERBB2 (HER2) gene amplification. The absence of standard gene mutations rendered it unresponsive to treatment with BRAF and MEK inhibitors. This molecular finding is rare in melanomas and represented a therapeutic target for off-label systemic treatment with drugs, primarily aimed at ERBB2 positive breast, gastric, and gastroesophageal junction cancers. A rare finding like this justifies molecular genetic analysis of unusual tumor specimen and guarantees optimal treatment for uncommon types of cardiac metastatic tumors.

Corticosteroid-induced immunodeficiency in a patient with gliomatosis cerebri: Are corticosteroids indicated in all brain tumors?

An elderly male was admitted to the Department of Neurology for slowly progressive dysarthria and right-sided atactic hemiparesis. Magnetic resonance imaging (MRI) revealed a small contrast-enhanced focus of malignant glioma in the left parietal lobe - with the growth pattern of cerebral gliomatosis - involving the whole left cerebral hemisphere, the corpus callosum, and spreading into the right frontal hemisphere. Diagnostic biopsy was deferred until the exclusion of other possible causes of the brain lesion. A follow-up brain MRI was planned in 6 weeks. In the interim, the patient was treated with dexamethasone, with mild improvement of the neurological symptoms. He was discharged home with a date for a follow-up brain MRI. One week later, the patient was readmitted due to a deterioration of speech and severe respiratory distress. The repeat brain MRI showed regression of contrast enhancement and no progression of the diffuse growth. Laboratory tests demonstrated tracheal candidiasis, invasive aspergillosis, and disseminated strongyloidiasis, including the brain. The patient rapidly deteriorated and died 11 days after the 2nd admission. The autopsy confirmed a small focus of glioblastoma in the left parietal lobe with the diffuse growth pattern of cerebral gliomatosis, laryngeal candidiasis, diffuse alveolar damage, with angioinvasive aspergillosis in the lungs and heart, and disseminated strongyloidiasis.

Coronary Artery Embolism From a Blood Cyst of the Mitral Valve.

Blood cysts are benign, congenital tumours of the heart endothelium, found most commonly on heart valves. Adult cases are rare, since most spontaneously regress with age. However, reports of symptomatic cases with embolic phenomena and valve dysfunction have been described. We present a case of a previously healthy 44-year-old woman with no cardiovascular risk factors who developed acute myocardial infarction caused by coronary artery embolism from a blood cyst of the anterior mitral valve leaflet.

Dilated cardiomyopathy and ovarian dysgenesis in a patient with Malouf syndrome: a case report.

Malouf syndrome is a rare congenital disorder involving the heart, genitalia, skin and skeletal characteristics. In the present study, we report on the sporadic case of a young female with dilated cardiomyopathy, hypergonadotropic hypogonadism, a small chin, bilateral blepharoptosis, marfanoid elongated fingers and hypothyroidism. Malouf syndrome may be caused by heterozygous mutations in the lamin A/C (LMNA) gene. Genetic analyses and autopsy were performed. In spite of the patient's features, sequence analysis of the coding region of the LMNA gene including exon-intron boundaries identified only one benign polymorphism: homozygous silent variant 1698C>T (H566). There is a possibility that the sequence analysis may have not detected intronic mutations or mutations in portions of the 5'- and 3'-untranslated regions, which would confirm the clinical diagnosis.

Native valve endocarditis due to Bartonella henselae in an immunocompetent man.

Culture-negative endocarditis accounts for 2.5-31% of all endocarditis cases and remains a diagnostic and therapeutic challenge. Bartonella spp. has only recently been recognized as an important cause of culture-negative endocarditis. We report a case of Bartonella henselae endocarditis occurring in an immunocompetent man who owned a cat and had previously been diagnosed with valvulopathy. Diagnosis was made only after prolonged diagnostic work-up with serology and with PCR and subsequent sequencing to identify the microorganism in the excised valves. The duration of treatment in patients with bartonella endocarditis is not clearly defined, and we decided to treat our patient with a prolonged course of antibiotic. Surgical treatment is usually necessary and was also successful in our patient. To our knowledge, this is the first case of bartonella endocarditis occurring in our geographic area.

Expression of cyclooxygenase-1 and cyclooxygenase-2 in the normal human heart and in myocardial infarction.

INTRODUCTION: Cyclooxygenase is a key enzyme in prostanoid synthesis. It exists in two isoforms: cyclooxygenase-1 (COX-1), which is constitutively expressed in cells and tissues maintaining normal homeostasis, and cyclooxygenase-2 (COX-2), which is normally not present in most cells, but can be induced by various stimuli. Little is known about the significance of COX isoforms in the normal human heart and in myocardial infarction (MI). Thus, we aimed to investigate the immunohistochemical expression of COX-1 and COX-2 in the normal human heart and in MI. METHODS: Our study included autopsy samples of heart tissue from 15 healthy individuals who died in accidents, and from 40 patients with MI who died few hours to a month after the onset of symptoms. Immunohistochemistry was performed by a sensitive peroxidase-streptavidin method on formalin fixed, paraffin-embedded tissue, using monoclonal antibodies against COX-1 and COX-2. RESULTS: In normal hearts, COX-1 was found in endothelial and smooth muscle cells of blood vessels and in endothelial cells of the endocardium. In MI, it was expressed in inflammatory cells, as well as in myofibroblasts and capillaries of granulation and fibrous tissue. COX-2 was either not present or it was present in occasional myocytes in the normal hearts. In MI, its expression was induced in cardiomyocytes as well as in interstitial inflammatory cells, and in capillaries and myofibroblasts in granulation tissue. CONCLUSIONS: Our results suggest that COX-1 is associated with normal homeostasis in the heart, whereas COX-2 probably mediates inflammatory reaction in MI. It appears that both COX-1 and COX-2 are associated with the healing processes and scar formation after MI.

Immunohistochemical expression of activated caspase-3 in human myocardial infarction.

There is mounting evidence that apoptosis is important in the pathogenesis of myocardial infarction (MI). One of the key events in the process of apoptosis is activation of caspase-3. Much attention has been recently paid to caspase inhibition as a potential treatment for ischemic cardiac disease. To predict the long-term effect of such treatment, it is essential to understand the significance of caspase-3 in the evolution of MI. Our aim was therefore to analyze immunohistochemical expression of activated caspase-3 in MI. Our study included autopsy samples of infarcted heart tissue from 50 patients with MI. Immunohistochemistry was performed by a sensitive peroxidase-streptavidin method on formalin-fixed, paraffin-embedded tissue, using monoclonal antibodies against activated (cleaved) caspase-3. We found caspase-3-positive myocytes in 18 MI less than 24 h old and in 3 MI that were presumably 48 h old. Their density (number of labeled myocytes/mm(2)) was greater in patients who received reperfusion treatment (mean 0.160+/-0.373 vs 0.025+/-0.037, p=0.06). In MI older than 48 h, positive reaction was observed in neutrophil granulocytes in the interstitium and, in subacute MI, it was observed in mononuclear inflammatory cells, myofibroblasts, and vascular endothelial cells. Our results suggest that apoptosis of myocytes is an important mode of cell death in the early MI, being enhanced in patients who received reperfusion treatment. After 48 h, apoptosis is an important mechanism of the clearance of neutrophil granulocytes and other inflammatory cells and of scar formation. Treatment with caspase inhibitors therefore will not only affect myocyte loss but will also interfere with the clearance of neutrophils and with the transformation of granulation tissue into a scar.

Peutz-Jeghers syndrome. A case report.

Peutz-Jeghers syndrome (PJS) is an unusual hamartomatous polyposis of the gastro intestinal (GI) tract, with pigmentation around lips and macules on the buccal mucosa. The case of a 10-year-old girl who presented with intussusception is reported. A polyp was found to be the cause of an invagination. Histologically it was a hamartoma. PJS is a rare syndrome inherited in an autosomal dominant pattern. Most patients have recurrent episodes of polyp induced bowel intussusception which requires repeated laparotomies. In addition, these patients have an increased risk of malignant disease in gastrointestinal and also non-gastrointestinal sites. To prevent cancer and short bowel syndrome, aggressive screening is recommended. Upper and lower endoscopy should be performed every two years from 10 years of age. Extra-intestinal surveillance for cancers, including abdominal and pelvic ultrasound, as well as testicular and breast examinations once yearly should be introduced in the second decade of life.

Childhood malignant blue nevus of the ear associated with two intracranial melanocytic tumors-metastases or neurocutaneous melanosis?

Blue nevus is an uncommon pigmented tumor of dermal melanocytes that has traditionally been classified into common and cellular variant. It is usually a skin tumor in adults but can become apparent in early childhood or even be present at birth. Malignant blue nevus is a rare melanocytic tumor of the skin arising from a preexisting cellular blue nevus. We report a multinodular blue nevus of the left ear in an 11-year-old girl who also had 2 intracranial melanocytic lesions. Differential diagnosis between metastases from malignant blue nevus and neurocutaneous melanosis is discussed.