Eumenia Costa da Cunha Castro

Prox-1 and VEGFR3 antibodies are superior to D2-40 in identifying endothelial cells of lymphatic malformations--a proposal of a new immunohistochemical panel to differentiate lymphatic from other vascular malformations.

We previously reported that D2–40 antibody identifies lymphatic endothelial cells (LECs) of lymphatic malformations (LM) with high specificity but only moderate sensitivity. The aim of this study was to compare the sensitivity and specificity of the markers Prospero-related homeobox gene–1 (Prox-1) and VEGFR3 to those of D2–40 for LECs in LM. Seventeen LM and 6 other vascular malformations with venous component (VM) were stained with D2–40, Prox-1, VEGFR3, CD31, and CD34 antibodies. The staining characteristics of vessels by each marker were assessed. Prox-1 and VEGFR3 specificity for LECs was examined by endothelial staining of VMs. Prox-1 and VEGFR3 stained substantially more large vessels than did D2–40 (15 of 17 cases). Small vessel staining was uniformly positive with all vascular markers except CD34, which did not stain lymphatic vessels. Eight cases had no or minimal D2–40 staining of large vessels, but the selected D2–40-vessels stained positive with VEGFR3, and 7 of 8 vessels were Prox-1 positive. Nine cases had variable D2–40 staining of large vessels; the selected D2–40 channels were all Prox-1 positive, and 8 of 9 were VEGFR3 positive. Two had rare vascular channels with no lymphatic marker stain but were positive for CD31 and CD34. Endothelial cells of VM had no Prox-1 but were VEGFR3/CD31/CD34 positive. VEGFR3 and Prox-1 antibodies have greater sensitivity for large lymphatic vessels than does D2–40. All lymphatic markers have high sensitivity for LECs of small lymphatic channels. Prox-1 has superior sensitivity and specificity to LECs. We recommend utilizing an immunohistochemical panel consisting of Prox-1, VEGFR3, CD31, and CD34 antibodies to differentiate lymphatic from venous malformations in pathologic practice.

Vocal Cord Basement Membrane in Non-Sudden Infant Death Syndrome Cases

ABSTRACT Vocal cord basement membrane thickening (VCBMT) has been observed in children with sudden infant death syndrome (SIDS). It has been proposed that this lesion could be used as a positive indicator of this syndrome in autopsies of children who have died unexpectedly. The present investigation aimed to analyze vocal cord basement membranes from autopsies of children 0 to 365 days old. A total of 134 larynges were analyzed. Histological sections of paraffin-embedded larynges stained with H&E and submitted to histochemical staining with periodic acid–Schiff (PAS), Massons trichrome, syrius red, and Carstairs were used for light microscopy analysis. Immunohistochemistry with monoclonal anti-collagen IV antibody was used to determine the nature of VCBMT. The study was completed with morphometry of H&E– and PAS-stained sections and revision of the clinical information contained in the hospital files. VCBMT was found in 25 cases (18.7%) and showed characteristics of normal basement membrane, including immunoreactivity to collagen IV. Our data support the conclusions that VCBMT is frequently seen in pediatric autopsies, is seen in children in all age-groups studied whose deaths were due to causes other than SIDS, and is commonly associated with infectious diseases. Like SIDS, VCBMT occurs in the first year of life.

Kocher-Debré-Sémélaigne syndrome diagnosed by autopsy associated with disseminated intravascular coagulation

Kocher-Debré-Sémélaigne syndrome is a rare disease with little literature, which develops with myopathy in infancy associated with neuromuscular alterations, polymyositis with symmetrical proximal muscle weakness, pseudohypertrophy, muscular rigidity and spasms, exercise intolerance, myxoedema, short stature, and cretinism. Male patient aged 18 years old, 1.52 m in height, admitted in the General Hospital of Triângulo Mineiro Federal University on November 11, 2003, complaining of intense diffuse abdominal pain like severe cramps, without triggering factors, associated with asthenia and hyporexia. This seems to be one of the few reports of KDS syndrome diagnoses by autopsy, where alterations in the thyroid gland connected with hypotrophy and probable congenital hypothyroidism were described and resulted in complications such as disseminated intravascular coagulation and hemophagocytic syndrome with fast progression to death of an 18-year-old patient.

Transcutaneous Electrical Nerve Stimulation and Placental Vascularization in Cases of Uterine Blood Flow Restriction

Studies report transcutaneous electrical nerve stimulation (TENS) as a treatment for placental insufficiency. To induce utero-placental insufficiency in rats, the uterine artery was ligated. Transcutaneous electrical nerve stimulation was applied with a frequency of 80 Hz, pulse duration of 200 μs, and low intensity. Placental blood vessels were analyzed after immunohistochemistry. The number, caliber and area occupied by placental vessels, fetal weight and length, and placental volume were lower in cases stimulated by TENS. The interaction between ligation and stimulation by TENS was associated with reduction of all these measurements, suggesting that TENS use during pregnancy may have harmful effects on intra-uterine development.

Foreskin analysis of circumcised boys with and without previous topical corticosteroid.

Problems with the foreskin are common reasons for pediatric surgery consultations. We collected the foreskin of 40 patients for 2 years and these samples were divided into groups with and without previous topical corticosteroid. We carried out histochemical hematoxylin & eosin and Picrosirius analyses of the foreskin. Collagen fibers and inflammatory infiltrate was higher in samples from patients who had complications related to phimosis. Fibrosis was higher in patients who used topical corticosteroid. A histopathologic study of the foreskin may provide an additional analysis of patients undergoing circumcision and it can also improve the accuracy of surgical indication.

The Anatomy of a Novel Malformation of the Cardinal Vein System

Anomalies of the cardinal vein system (CVS) are uncommon but if unidentified can lead to life-threatening complications. We report a case with a novel malformation of the CVS. Autopsy with in situ dissection of heart and large vessels in a 25-day-old infant was performed. The infant was diagnosed with congenital heart disease, and systemic venous malformations were suspected by imaging. Correlation between premortem imaging and postmortem anatomy was performed. The superior and inferior left venous systems developed abnormally. A persistent left superior vena cava (PLSVC) drained into the right atrium via the coronary sinus. A persistent left inferior vena cava (PLIVC) continued with the hemiazygos vein (HV), which drained into the PLSVC. The innominate vein was absent. The left renal vein was connected to the HV. Two common iliac veins were identified. The left drained into the PLIVC and the right into the right inferior vena cava (IVC). Perinatal echocardiography identified only the dilated HV draining to an LSVC and a small IVC. Congenital heart disease included hypoplastic left ventricle with hypoplastic aortic arch and subaortic stenosis, which were diagnosed by fetal ultrasound. Remodeling of components of CVS takes place during development, and unknown mechanisms guide this process. Defects of this process can lead to variable malformations, as demonstrated by this case. To our knowledge, the combination of complex malformations of both superior and IVC systems that extends to the common iliac veins has not been reported. We recommend identifying vascular anomalies in situ during autopsy before anatomic relationships are altered.

Morphologic analysis of fetal stress organsin different causes of perinatal death.

Complications act as stress-inducers during pregnancy so the fetus can develop functional compensatory mechanisms or morphologic changes. The cases analyzed are with congenital malformations or acute stress; chronic included cases with ascending infection (AI) and perinatal hypoxia/anoxia (PHA). The hematoxylin-eosin (H&E) was done to analyze the vacuolization, and the immunohistochemistry to the phagocytosis. The discreet standard of vacuolization was observed in 52.6% of the cases, 22.1% moderate, and 25.3% severe. The number of macrophages was higher in PHA. Changes in these organs are closely related to the cause of death and to the period during which the harmful agent.

Mucocele: A Human Model for Lymphangiogenesis

The mechanism of lymphangiogenesis is poorly understood, and controversy exists whether it is part of the inflammatory response to tissue injury. Utilizing markers specific to lymphatics, we aimed to study if lymphangiogenesis plays a role in the tissue response of mucoceles. Twenty-three extravasated mucoceles were selected. They were grouped by using widely accepted histologic criteria of wound healing into early-, intermediate-, and late-phase lesions. To identify lymphatic vessels we used lymphatic endothelium-specific antibodies (VEGFR3, Prospero-related homeobox gene–1 [Prox-1], and D2–40). To assess the proportion of lymphatic channels to all lesional vessels we used the panendothelial marker CD31. The presence, distribution, and proportion of lymphatic channels were assessed and compared among the groups. To investigate the involvement of lymphangiogenic signals, the expression of VEGFC was determined. To assess for proliferative activity of lymphatic endothelial cells we utilized Ki-67 antibody. Early-phase lesions (n = 6) were characterized by the presence of centrally located mucicarmine-positive material (mucin pools) with numerous inflammatory cells dominated by mucin-laden CD163-positive macrophages. Only scattered peripheral thin-walled large and small vessels were seen in the stroma surrounding the central mucin pool. Less than half of these vessels were of lymphatic nature as determined by Prox-1, VEGFR3, and D2–40 positivity. The histology of the intermediate-phase lesions (n = 6) was dominated by numerous lymphatics of varying size, not seen in the early phase. The histology of late-phase lesions (n = 11) resembled a “pseudo-cyst,” with dense granulation tissue containing rare macrophages and rare lymphatic vessels. Although VEGFC was present in all phases, the highest expression was in the early phase. Low-grade proliferative lymphatic endothelium was noted in the intermediate lesions with a Ki-67 index of 4%. Early lymphangiogenesis and late lymphatic vessel regression were observed during mucocele evolution. The abundant newly formed ectatic lymphatic vessels seen in the intermediate phase may play a role in the clearance of extravasated material (mucin, edema, and lymph fluid) and in the initiation of the young fibroblast-rich granulation tissue. Mucocele appears to be an excellent human model for studying the factors that play a role in new lymphangiogenesis and regression.

Primary mesenteric angiosarcoma in a child with associated lymphangiectasia: A case report

Angiosarcomas are rare tumors in children, usually occurring in soft tissue and liver. By contrast, angiosarcoma in adults usually occurs in the extremities in conjunction with lymphedema. Mesenteric angiosarcoma has only rarely been reported. When angiosarcomas arise in this location, they usually represent a 2nd malignancy following Hodgkins lymphoma. We report a child who presented to the emergency room with an acute abdomen and underwent emergency surgery for a mesenteric angiosarcoma with associated lymphangiectasia of the bowel and mesentery. A brief review of the literature and the nomenclature of these unusual tumors are discussed.

Mucous gland adenoma of the bronchus in a 5-year-old child: case report and review of the literature

O adenoma de celulas mucosas e uma neoplasia benigna rara que se origina nas glândulas da mucosa das vias aereas maiores. A maioria dos casos e vista nos bronquios, mas ja foram descritos casos na traqueia e nas vias respiratorias distais. O tumor e constituido por celulas mucossecretoras, que geralmente formam glândulas que crescem para dentro da luz, formando massa obstrutiva. Nao ha predilecao por sexo ou idade. Nos relatamos aqui um caso observado em uma menina de 5 anos, o mais jovem relato na literatura consultada, que se apresentou no Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto para investigacao e tratamento de pneumonia recorrente e atelectasia do pulmao. O exame broncoscopico mostrou massa obstruindo o bronquio inferior esquerdo e a biopsia revelou lesao benigna incaracteristica. A remocao cirurgica do segmento afetado, que e o tratamento recomendado para esta lesao benigna, evidenciou um adenoma de celulas mucosas. A crianca recuperou-se bem e estava completamente livre de doenca quando deixou o seguimento com 6 anos de idade.