Clinical and histologic characteristics of clinically unsuspected melanomas.

Thin melanomas are recognized and captured by clinicians at an alarming rate, whereas thick melanomas remain underrecognized. Improved recognition of thick melanomas will require further understanding of their clinical and histologic characteristics at various stages of development because emerging data suggest that the thin melanomas being captured today may not represent the forerunners of the thick melanomas. In this retrospective analysis, pathology requisition forms from melanomas diagnosed by histopathology were examined for submitted clinical diagnosis, patient characteristics, melanoma thickness, and biopsy method. Three hundred eighty-five melanomas were identified from 2003 to 2011. Most lesions (71.7%) were clinically suspected to be melanocytic. The mean depth in this group was 0.62mm. Of the unsuspected cases (28.3%), the most common submitted diagnoses were basal cell carcinomas and seborrheic keratoses, consistent with previous reports. The mean depth in the unsuspected group was 1.64mm, and more frequently extended to the deep margin (51.8% vs 25.4% of the time). Shave biopsy was the overwhelming preferred method of biopsy (79.5% overall). Compared with thin melanomas, thick melanomas are underrecognized by physicians due to their lack of characteristic morphologic features; consequently, they are more frequently associated with suboptimal biopsies.

Association of thymectomy with infection following congenital heart surgery.

BACKGROUND: Congenital absence of the thymus can lead to profound immunodeficiency, suggesting that thymic function during fetal development is essential to normal lymphocyte development. How vital the thymus after birth is to human immune competence and regulation is not known. Routine thymectomy, especially at an early age, may influence immunity, and therefore the risk of infection, autoimmunity, or malignancy. METHODS: A retrospective review of cardiac surgery patients followed at Seattle Children's Hospital was performed. The primary outcome was rate of serious infections requiring hospitalization. Secondary analyses included age, type of infection, cardiac diagnosis, surgical procedure, and comorbidities. RESULTS: Patients fell into 2 groups: 60 with complete thymectomy and 35 with partial or no thymectomy. There was no statistical difference between groups in the overall prevalence of serious infections (16.7% vs 17.2%, P = 1.0). There was a nonsignificant trend toward reduced time between surgery and onset of first infection in patients in the total thymectomy group versus those without thymectomy (1.7 years vs 4.6 years, P = .07). Total thymectomy before 6 months of age also tended to increase infection rate, but the effect was not significant (0.09/year vs 0.02, P = .14). Gastroesophageal reflux in patients with total thymectomy increased the risk of infection (P = .013), suggesting a cumulative effect. CONCLUSIONS: Though infections occurred frequently in the childhood cardiac surgery population, total thymectomy was not associated with increased risk of serious infection. Comorbid conditions may be more important contributing factors increasing the risk of infection in this complex and vulnerable population.

Chimeric maternal cells with tissue-specific antigen expression and morphology are common in infant tissues.

Maternal microchimerism (MMc) has been purported to play a role in the pathogenesis of autoimmunity, but how a small number of foreign cells could contribute to chronic, systemic inflammation has not been explained. Reports of peripheral blood cells differentiating into tissue-specific cell types may shed light on the problem in that chimeric maternal cells could act as target cells within tissues. We investigated MMc in tissues from 7 male infants. Female cells, presumed maternal, were characterized by simultaneous immunohistochemistry and fluorescence in situ hybridization for X- and Y-chromosomes. Maternal cells constituted 0.017% to 1.9% of parenchymal cells and were found in all infants in liver, pancreas, lung, kidney, bladder, skin, and spleen. Maternal cells were differentiated: maternal hepatocytes in liver, renal tubular cells in kidney, and beta-islet cells in pancreas. Maternal cells were not found in areas of tissue injury or inflammatory infiltrate. Maternal hematopoietic cells were found only in hearts from patients with neonatal lupus. Thus, differentiated maternal cells are present in multiple tissue types and occur independently of inflammation or tissue injury. Loss of tolerance to maternal parenchymal cells could lead to organ-specific "auto" inflammatory disease and elimination of maternal cells in areas of inflammation.

Male microchimerism in women without sons: quantitative assessment and correlation with pregnancy history.

PURPOSE: Fetal microchimerism, derived from fetal cells that persist after pregnancy, is usually evaluated by tests for male microchimerism in women who gave birth to sons. We investigated male microchimerism in women without sons and examined correlation with prior pregnancy history. Immunologic consequences of microchimerism are unknown. We studied healthy women and women with rheumatoid arthritis (RA). METHODS: Y-chromosome-specific real-time quantitative polymerase chain reaction was used to test peripheral blood mononuclear cells of 120 women (49 healthy and 71 with RA). Results were expressed as the number of male cells that would be equivalent to the total amount of male DNA detected within a sample containing the equivalent of 100000 female cells. RESULTS: Male microchimerism was found in 21% of women overall. Healthy women and women with RA did not significantly differ (24% vs 18%). Results ranged from the DNA equivalent of 0 to 20.7 male cells per 100000 female cells. Women were categorized into 4 groups according to pregnancy history. Group A had only daughters (n = 26), Group B had spontaneous abortions (n = 23), Group C had induced abortions (n = 23), and Group D were nulligravid (n = 48). Male microchimerism prevalence was significantly greater in Group C than other groups (8%, 22%, 57%, 10%, respectively). Levels were also significantly higher in the induced abortion group. CONCLUSIONS: Male microchimerism was not infrequent in women without sons. Besides known pregnancies, other possible sources of male microchimerism include unrecognized spontaneous abortion, vanished male twin, an older brother transferred by the maternal circulation, or sexual intercourse. Male microchimerism was significantly more frequent and levels were higher in women with induced abortion than in women with other pregnancy histories. Further studies are needed to determine specific origins of male microchimerism in women.

Myocardial-tissue-specific phenotype of maternal microchimerism in neonatal lupus congenital heart block.

BACKGROUND: During pregnancy, maternal cells pass into the fetus, where they can persist for many years after birth. We investigated the presence of maternal cells in neonatal lupus syndrome (NLS), an autoimmune disease that develops in utero. The most serious complication of NLS is inflammation of the atrioventricular node leading to congenital heart block (CHB). METHODS: In a blinded case-control study, maternal (female) cells were detected and quantified in male NLS and control heart-tissue samples. We used fluorescence in-situ hybridisation to label X and Y chromosomes. Studies in transplantation suggest that donor cells can differentiate into somatic tissue cells. Therefore, we asked whether maternal cells transferred in utero have cellular plasticity. To simultaneously identify and characterise maternal cells, we developed a technique by which multiple phenotypic markers could be detected concurrently with fluorescence in-situ hybridisation in the same cells of a tissue section. FINDINGS: Maternal cells were found in 15 of 15 sections of NLS heart tissue, ranging from 0.025% to 2.2% of total cells. By contrast, maternal cells were found in two of eight control sections (0-0.1%). Very few maternal cells expressed the haemopoietic cell marker CD45. Most expressed sarcomeric alpha actin, a specific marker for cardiac myocytes. INTERPRETATION: Our findings suggest that differentiated tissue-specific maternal microchimerism can occur in neonates. Thus, semiallogeneic maternal cells could be the target of an immune response. Alternatively, maternal cells could contribute to a secondary process of tissue repair.