Mutational Analysis of Portuguese Families with Multiple Endocrine Neoplasia Type 1 Reveals Large Germline Deletions

OBJECTIVE: To determine the spectrum of MEN1 mutations in Portuguese kindreds, and identify mutation-carriers. PATIENTS, DESIGN AND RESULTS: Six unrelated MEN1 families were studied for MEN1 gene mutations by single-strand conformational polymorphism (SSCP) and DNA sequence analysis of the coding region and exon-intron boundaries of the MEN1 gene. These methods identified 4 different heterozygous mutations in four families: two mutations are novel (mt 1539 delG and mt 655 ims 11 bp) and two have been previously observed (mt 735 del 46p and mt 1656 del C) all resulting in a premature stop codon. In the remaining two families, in whom no mutations or abnormal MEN1 transcripts were detected, segregation studies of the 5' intragenic marker D11S4946 and codon 418 polymorphism in exon 9 revealed two large germline deletions of the MEN1 gene. Southern blot and tumour loss of heterozygosity analysis confirmed and refined the limits of these deletions, which spanned the MEN1 gene at least from: exon 7 to the 3' untranslated region, in one family, and the 5' polymorphic site D11S4946 to exon 9 (obliterating the initiation codon), in the other family. Twenty-six mutant-gene carriers were identified, 6 of which were asymptomatic. CONCLUSIONS: These results emphasize the importance of the detection of MEN1 germline deletions in patients who do not have mutations of the coding region. Important clues indicating the presence of such deletions may be obtained by segregation studies using the intragenic polymorphisms D11S4946 and at codon 418. The detection of these mutations will help in the genetic counselling of clinical management of the MEN1 families in Portugal.

Tumores do Corpo Carotídeo. Experiência de um Serviço no Diagnóstico e Tratamento nos Últimos 10 Anos

INTRODUCTION: Carotid body tumours (CBT) are neoplasms that develop from paragangionic cells of this structure. They are rare, with an estimated incidence of 1:30000 and can be associated with other neuro-endocrine neoplasia. The authors report their experience in the management of the disease, in the last 10 years. MATERIAL AND METHODS: Eight patients (with eight tumours) were treated, all submitted to tumour resection. 75% were female and the mean age was 56 years. We report a 12,5% incidence of neurological sequelae from surgery, and no mortality. In the follow-up (which varied between 1 and 10 years), no local or contralateral recurrence or metastasis were registered. Also, we did not found family cases of this disease. CONCLUSIONS: The authors noticed an unusually high proportion of female patients. The tumour resection was curative in all patients, with a rate of neurological complications inferior to that reported in other published series. These neurological sequelae were reported in patients with large tumours, thus reinforcing the outmost importance of an early diagnosis. Pre-operative selective embolization of these tumours can be helpful in the resection of large tumours, allowing a potential reduction in neurological complications.

A Utilização de Endopróteses na Síndrome da Veia Cava Superior por Neoplasia do Pulmão

Apresentam-se seis casos de síndrome da veia cava superior causado por neoplasia do pulmão e que foram tratados por endopróteses colocadas por via percutânea. Descreve-se a técnica e avaliam-se os resultados. Num caso ocorreu trombose aguda da endoprótese que foi tratada por uroquinase. Não se registaram outras complicações. Um doente faleceu 1 mês depois por progressão da doença. Os restantes mantinham-se sem queixas de síndrome da veia cava superior durante mais do que 6 meses. Conclui-se que a colocação de endopróteses é uma técnica pouco invasiva, eficaz e com melhoria imediata no síndrome da veia cava superior.

Burkitt’s Lymphoma Related to Epstein–Barr Virus Infection During Pregnancy

Setting: Burkitt’s lymphoma is a rare form of cancer and is an extremely rare diagnosis during pregnancy. This form of lymphoma is a very fast growing B cell neoplasm and chemotherapy is the treatment of choice for the disease in all its stages. Case report: The authors describe the case of a Caucasian 40-year-old nulliparous woman, with previous known Epstein–Barr virus infection, that presents at 28 weeks gestation with supraclavicular adenopathy and multiple bilateral breast nodules, in which biopsy showed non-Hodgkin lymphoma, Burkitt’s type. Discussion: There are few described cases of Burkitt’s lymphoma during pregnancy and in general the outcomes have been poor. In most of the cases, the patients were not treated by current standards or instead had a late diagnosis. This neoplasia is the most rapidly progressive human tumor, and any delay in initiating therapy can adversely aVect patient’s prognosis. The authors discuss treatment options in pregnancy and its perinatal implications.

Oral Contraceptive Use and Clinical Outcomes in Patients with Multiple Sclerosis

Experimental and clinical data suggest a role of sex steroids in the pathogenesis of multiple sclerosis (MS). Scant information is available about the potential effect of oral contraceptive (OC) use on the prognosis of the disease. We aimed to evaluate this. The study population consisted of 132 women with relapsing-remitting MS before receiving disease modifying treatment and a mean disease duration 6.2 (SD 5.1) years. Three groups of patients were distinguished according to their OC behavior: [1] never-users, patients who never used OC [2] past-users, patients who stopped OC use before disease onset, and [3] after-users, those who used these drugs after disease onset. Multiple linear and logistic regression models were used to analyze the association between oral contraceptive use and annualized relapse rates, disability accumulation and severity of the disease. After-user patients had lower Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) values than never users (p<0.001 and p=0.002, respectively) and past users (p=0.010 and p=0.002, respectively). These patients were also more likely to have a benign disease course (MSSS<2.5) than never and past users together (OR: 4.52, 95%CI: 2.13-9.56, p<0.001). This effect remained significant after adjustment for confounders, including smoking and childbirths (OR: 2.97, 95%CI: 1.24, 6.54, p=0.011 and for MSSS β: -1.04; 95% C.I. -1.78, -0.30, p=0.006). These results suggest that OC use in women with relapsing-remitting MS is possible associated with a milder disabling disease course.

Blastic Plasmacytoid Dendritic Cell Neoplasm

Blastic plasmacytoid dendritic cell neoplasm is a rare and aggressive hematodermic neoplasia with frequent cutaneous involvement and leukemic dissemination. We report the case of a 76-year-old man with a 2 month history of violaceous nodules and a tumor with stony consistency, located on the head, and mandibular, cervical and supraclavicular lymphadenopathies. Multiple thoracic and abdominal adenopathies were identified on computerized tomography. Flow cytometry analysis of the skin, lymph node and bone marrow biopsies demonstrated the presence of plasmocytoid dendritic cell neoplastic precursor cells (CD4+, CD45+, CD56+ and CD123+ phenotype). After initial clinical and laboratorial complete remission with chemotherapy, the patient died due to relapse of the disease associated with the appearance of a cervical mass with medullary compromise.

Phaeohyphomycosis Caused by Alternaria Infectoria Presenting as Multiple Vegetating Lesions in a Renal Transplant Patient

The genus Alternaria is one of the most common black moulds and appears to be increasing as a causative agent of subcutaneous phaeohyphomycosis, particularly among immunosuppressed patients. A 53-year-old patient who had received a kidney transplant presented with multiple verrucous lesions on the distal extremities. Positive histopathology and cultures, in addition to rDNA ITS region sequencing, identified the fungal isolate as Alternaria infectoria. Oral itraconazole was administered for 10 months. A follow-up at 15 months demonstrated no signs of infection. Clinical manifestations of cutaneous alternariosis vary significantly and only a few cases have been described in the literature. Although optimal treatment options remain controversial, this case of phaeohyphomycosis was successfully treated with itraconazole monotherapy.

Utilidade da Broncofibroscopia no Diagnóstico de Neoplasia do Pulmão em Doentes com Pneumonia Arrastada

A broncofibroscopia (BF) é frequentemente efectuada em doentes com pneumonias de evolução arrastada com o objectivo de excluir patologia endobrónquica de etiologia neoplásica. Dado que a resolução radiográfica das pneumonias da comunidade é variável, sendo dependente de vários factores (agente etiológico, idade, doenças associadas) a decisão para efectuar uma BF é muitas vezes empírica. Com o objectivo de descrever a nossa experiência neste problema estudámos retrospectivamente 123 doentes com o diagnóstico de pneumonia da comunidade baseado em critérios clínicos e radiográficos e que, apesar da antibioferapia considerada adequada, não apresentavam melhoria radiográfica significativa ao fim de pelo menos 2 semanas. Obtivemós um diagnóstico histológico de neoplasia maligna do pulmão em 7 doentes (5,6° o), sendo todos do sexo masculino, com idade superior a 55 anos efuínadores de pelo menos 40 U.M.A. A análise comparativa com os restantes doentes mostrou diferenças com significado~estatístico em relação à idade e ao consumo tabágico. O tempo de evolução da doença,valores médios de hemoglobina, leucocitos, VS, existência ou não de alterações da função renal ou hepática não foram significativamente diferentes nos dois grupos. Concluimos que a BF deve ser efectuada precocemente nos doentes pertencentes ao grupo de risco identificado (fumadores, com mais de 55 anos) não se justificando a sua realização nos restantes doentes antes das 4 a 8 semanas de evolução, a menos que estejam presentes critérios clínicos objectivos tais como progressão da doença ou agravamento do estado geral.

Multiple Mechanical Complications in ST-Segment Elevation Myocardial Infarction with Angiographically Normal Coronary Arteries

This case report discusses an unusual presentation of ST-segment elevation myocardial infarction (STEMI) with normal coronary arteries and severe mechanical complications successfully treated with surgery. An 82-year-old man presented STEMI with angiographically normal coronary arteries and no major echocardiographic alterations at discharge. At the first month follow-up, he complained of fatigue and dyspnea, and contrast echocardiography complemented by cardiac magnetic resonance imaging revealed a large left ventricular apical aneurysm with a thrombus communicating by two jets of a turbulent flow to an aneurysmatic formation of the right ventricular apex. The patient underwent a Dor procedure, which was successful. Ventricular septal defects and ventricular aneurysms are rare but devastating complications of STEMI, with almost all patients presenting multivessel coronary artery disease. Interestingly in this case, the angiographic pattern was normal.

Multiple Sclerosis and Motherhood Choice: an Observational Study in Portuguese Women Patients

INTRODUCTION. Multiple sclerosis (MS) is a disabling disease occurring mainly in women of childbearing age. MS may interfere with family planning and motherhood decision. AIM. To study the influence of MS diagnosis and course of the disease on motherhood decision. PATIENTS AND METHODS. The cohort of 35 to 45-year-old female patients diagnosed with MS for at least ten years was selected from six Portuguese MS centers. A structured questionnaire was applied to all patients in consecutive consultation days. Clinical records were reviewed to characterize and collect information about the disease and pregnancies. RESULTS. One hundred women were included; mean age at MS diagnosis was 26.3 ± 5.0 years; 90% of the participants presented with a relapsing-remitting MS; 57% had no pregnancies after the diagnosis. MS type and number of relapses were not significantly different between women with or without pregnancies after the diagnosis (p = 0.39 and p = 0.50, respectively). Seventy-seven percent of the patients did not have the intended number of pregnancies. Main reasons given were fear of future disability and the possibility of having relapses. Forty-three women considered that pregnancy might worsen MS. CONCLUSION. In our population, motherhood choice was unrelated to the MS type and the number of relapses. However, a relevant number of women had fewer pregnancies than those intended before MS diagnosis and believed that pregnancy could worsen the disease. An effort to better inform the patients should be made to minimize the impact of MS diagnosis on motherhood decision.

Multiple Haemangiomas, Diaphragmatic Eventration and Beckwith-Wiedemann Syndrome: An Unusual Association

A 6-month-old girl with Beckwith-Wiedemann syndrome, multiple haemangiomas (axillary, laryngeal, pulmonary and hepatic) and diaphragmatic eventration was reported. All tumours responded to treatment with propranolol. The surgical correction of diaphragmatic eventration was crucial to a better outcome.