Tracheomalacia in a neonate with kniest dysplasia: histopathologic and ultrastructural features

Kniest dysplasia is an autosomal-dominant chondrodysplastic condition characterized by disproportionate dwarfism, short trunk, small pelvis, kyphoscoliosis, short limbs, prominent joints, premature osteoarthritis, and craniofacial manifestations. The craniofacial abnormalities include tracheomalacia, midface hypoplasia, cleft palate, early onset myopia, retinal detachment, prominent eyes, and sensorineural hearing loss. Radiologic features include dumbbell-shaped femora, platyspondylia with anterior wedging of vertebral bodies, coronal clefts of thoracolumbar vertebral bodies, low broad ilia, and short tubular bones with broad metaphyses and deformed large epiphyses. This form of chondrodysplasia is associated with mutations in type II collagen splicing sequences. Mutations have been identified in the COL2A1 (type II collagen) gene between exons 12 and 24. Type II collagen is the predominant structural protein in cartilage, and mutations in this collagen account for the Kniest dysplasia phenotype. Histopathologic and ultrastructural features of epiphyseal plate cartilage have been described, but tracheal cartilage in an affected neonate has not been examined. The authors report the histopathologic and ultrastructural findings of anterior tracheal cartilage from a 35-day-old female with suspected chondrodysplasia who had tracheomalacia with airway obstruction. The tracheal cartilage was moderately cellular, but lacked cystic and myxoid changes in its matrix. The chondrocytes had abundant cytoplasmic PAS-positive inclusions. Some of these inclusions were diastase-resistant and were also highlighted on Alcian blue staining. Ultrastructural examination revealed chondrocytes with greatly dilated rough endoplasmic reticulum containing granular proteinaceous material. There were also frequent aggregates of typical glycogen. The defect in the COL2A1 gene is secondary to mutations, especially at splice junctions, and this markedly disrupts triple helix formation. The mutated type II procollagen results in intracellular retention within the chondrocytes, as abundant granular proteinaceous material within the dilated RER. A relationship is known to exist between the proportion of mutated to normal type II collagen in the matrix and the severity of the phenotype. With low levels of normal type II collagen, the phenotypic manifestations become more severe, such as in achondrogenesis type II. Both the quantity and quality of type II collagen modulates the phenotypic expression of type II collagenopathies.     

The Ultrastructural and Histophotometric Study of Elastic and Collagen Fibers in Type II Ehlers-Danlos Syndrome and Subclinical Forms

Skin disorders in type II Ehlers-Danlos Syndrome (EDS) are characterized by signs of cutaneous hyperdistensibility, skin and vascular fragility, atrophic scars, and articular hypermobility. These features may have less important clinical presentation in the intermediate forms of type II EDS. The authors studied the ultrastructural and quantitative aspects of elastic and collagen fibers in the skin of individuals with subclinical signs of type II of Ehlers-Danlos Syndrome. A group of 27 individuals (Group I) with large atrophic scars, articular hypermobility of the hands, and cutaneous and vascular fragility were compared with 10 healthy individuals. The subjects from both groups were volunteers from Hospital das Clínicas da Universidade de São Paulo. The elastic fibers did not show alterations but collagen ultrastructural abnormalities were seen in diameter and curvature, such as torsion, collagen flower-like aspect and discrete mass enlargement by histophotometry.     

Lipoblastoma and Lipoblastomatosis in Infancy and Childhood: Histopathologic,Ultrastructural, and Cytogenetic Features

Lipoblastoma is a relatively rare tumor that occurs in infancy and early childhood and arises from embryonic white fat. Although a benign tumor, lipoblastomas tend to recur and may resemble myxoid liposarcoma. The authors report 26 cases over a 15-year period at Texas Children's Hospital. There was a slight female predilection (14F:12M). The most common symptom was a painless mass with or without increasing size. The trunk, extremities, head and neck, retroperitoneum, inguinal canal, peritoneal cavity, and lung were the tumor sites. Most tumors were circumscribed lipoblastomas and the minority were diffuse infiltrative lipoblastomatosis. Reexcision for residual or recurrent tumor was necessary more frequently in patients with lipoblastomatosis. Histopathologic examination and ultrastructural examination revealed cellular neoplasms composed of immature adipocytes with relatively well-defined septa, frequent lipoblasts, a fine vascular network, and often a myxoid appearance resembling myxoid liposarcoma. Cytogenetics was performed in 4 cases with chromosome 8q abnormality being most common. The major concern with lipoblastoma in children is to completely excise the tumor to avoid leaving residual tumor and to prevent recurrences. Confusion with myxoid liposarcoma, well-differentiated liposarcoma, and typical lipomas may occur. Although asymptomatic, lipoblastomas may cause dysfunction of other organ systems due to mass effect. Complete surgical excision with at least 2 years of follow-up is the preferred therapy.     

Intercellular Junctions,Apical Differentiation,and Infiltrative Features in Colon Cancer: An Ultrastructural Study

Changes in the structure and number of cell junctions have been related to the infiltrative and metastatic potential of tumor cells. Apparently, the loss of cell adhesion should be coordinated with significant changes in the apical and basal cell domains. The authors have performed a sequential ultrastructural study of cells in the superficial, middle, and deep regions of well- and moderately differentiated colon adenocarcinomas. This was to investigate the differencesin the organization of different membrane domains among tumor cells in the in situ areas, the advancing, infiltrative edge of the tumors, and the infiltrating zones between these two extreme zones. The results of the study suggest that the organization of these domains is not strictly coordinated, and that, for each infiltration level, both a settling and an infiltrating cell population can be found. These findings could explain the fact that apparently well-differentiated tumors are able to seed distant tissues with individual cells, rather than with well-differentiated glandular aggregates that would hardly be able to reach the vessel lumina without significantly modifying their organization.     

Spindle Cell Carcinoids of the Lung with Paraganglioid Features: a Reappraisal of their Histogenetic Origin from Paraganglia Using Immunohistochemical and Electronmicroscopic Techniques

Five cases of spindle cell carcinoids of the lung were analyzed by immunohistochemical and ultrastructural technique. They were found to be biphasic tumors composed of the major component of neuroendocrine cells (chief cells) and a minor component of dendritic cells (supporting cells). The chief cells displayed positivity for neuroendocrine phenotypic antigenic markers: neuron specific enolase (NSE), chromogranin A, and synaptophysin. They contained varying numbers of dense-core granules by electron microscopy. In addition, the chief cells expressed cytoplasmic positivity for cytokeratins. The supporting cells were dendritic in appearance and displayed strong positivity for S-100 protein in all cases. Glial fibrillary acidic protein was positive in two cases. On electron microscopy, the supporting cells were agranular and found along the external lamina surrounding the nests of tumor cells. In two cases, rare ganglion cell-like cells were present. The histomorphologic, immunohistochemical, and ultrastructural features were contrastingly different from the classical pulmonary carcinoid and rather resembled gangliocytic paragangliomas arising from small intestine and spine. It is proposed that pulmonary carcinoids with biphasic features are better designated as gangliocytic paragangliomas of the lung rather than paraganglioid carcinoids.