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.     

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.     

Epithelioid Variant of Pleomorphic Liposarcoma: A Comparative Immunohistochemical and Ultrastructural Analysis of Six Cases with Emphasis on Overlapping Features with Epithelial Malignancies

Pleomorphic liposarcoma (PL) is the least common subtype of liposarcoma, displaying a lipoblastic, malignant fibrous histiocytoma (MFH)-like and, less frequently, an epithelioid growth pattern. The epithelioid morphology in PL is still underrecognized and may closely simulate other epithelial neoplasms, mainly adrenal cortical carcinoma (ACC). No electron microscopic (EM) studies of the epithelioid variant of PL have been previously described, nor have there been studies of its immunoreactivity with A103 or &#102 -inhibin. The purpose of this study is to analyze the histological, immunohistochemical, and EM features of epithelioid PL in an attempt to better explore the distinction from their epithelial mimickers, such as ACC. A panel of 5 antibodies was studied, including A103, &#102 -inhibin, smooth muscle actin (SMA), AE1/AE3, and Cam 5.2. Out of 22 cases of PLs, 6 cases characterized by the presence of both epithelioid phenotype and pleomorphic lipoblasts were identified from the EM archives. There were 4 females and 2 males, with a mean age of 58 (range, 39-78). Two lesions arose in the thigh and 1 each in the abdominal wall, chest wall, anterior mediastinum, and retroperitoneum, with tumor size ranging from 7 to 17 cm (mean, 13 cm). Histologically, 2 PLs were pure epithelioid, whereas the other 4 had a mixed epithelioid and MFH-like appearance. Immunohistochemically, A103 (4/6), SMA (4/6), and AE1/AE3 (1/6) revealed a various degree of positive reactions. No immunolabeling for &#102 -inhibin or Cam5.2 was detected in any case. By EM, the epithelioid areas revealed round or polyhedral cells with lipid droplets of various sizes and number, intimately apposed cell surfaces, occasional junction-like structures (4/6), and micropinocytotic vesicles (4/6). Interestingly, the ribosome-lamellar complexes, once thought to be characteristic of hairy cell leukemia but rarely seen in solid tumors, were noted in one pure epithelioid PL. When compared to the MFH-like area, rough endoplasmic reticula (RER) were less well developed, but mitochondria were more prominent in the epithelioid components. Neither mitochondria with tubulovesicular cristae nor prominent smooth endoplasmic reticula indicative of ACC were seen. Well-formed external lamina was not present. Other features to support a higher level of epithelial differentiation, such as lumen formation, microvilli, and tonofilaments, were not found. In conclusion, focal A103 reactivity in epithelioid undifferentiated tumors should be interpreted with caution before rendering the diagnosis of a primary or metastatic ACC, especially when examining biopsy specimens. The possibility of an epithelioid variant of PL must be excluded; &#102 -inhibin can serve as a useful adjunct in this regard. In addition to variable intracytoplasmic fat droplets, the distinctive ultrastructural features of epithelioid variant of PL include numerous mitochondria, pinocytotic vesicles, junction-like structures, and, rarely, ribosome-lamellar complex. Despite some overlapping features, electron microscopy remains a useful tool to distinguish between epithelioid PL and ACC.     

Mixed-type liposarcoma: clinicopathological, immunohistochemical, and molecular analysis of a case arising in deep soft tissues of the lower extremity

A rare case of mixed-type liposarcoma arising in deep soft tissue of the right thigh of a 45-year-old female patient is reported. The neoplasm was completely excised and was composed of an irregular admixture of areas of atypical lipomatous tumor/well-differentiated liposarcoma of the lipoma-like subtype with areas of myxoid/round cell liposarcoma. An amplification of the MDM2 and CDK4 genes respectively in the atypical lipomatous tumor/well-differentiated liposarcoma areas was detected by fluorescence in situ hybridization (FISH) analysis, and translocations of the CHOP and FUS genes were detected by FISH analysis in the myxoid/round cell liposarcoma areas.     

Pituitary Adenoma in Carney Complex: An Immunohistochemical,Ultrastructural, and Immunoelectron Microscopic Study

First described in 1985, Carney complex is a rare, heritable disorder featuring abnormal skin pigmentation, cardiac and cutaneous myxoma, melanotic schwannoma of psammomatous type, and endocrine abnormalities, including pituitary adenomas. Patients with the latter present with elevated growth hormone (GH) levels and acromegaly or gigantism. Prolactin (PRL) elevation may also be seen. The authors have investigated 2 resected pituitary adenomas from patients with Carney complex. One, a 19-year-old female acromegalic with elevated GH, IgF-1, and PRL levels, had a mammosomatotroph adenoma immunoreactive for GH and PRL. Ultrastructurally, GH and PRL were present in the same secretory granules. The second patient, a 27-year-old acromegalic, had a sparsely granulated GH cell adenoma that by immuno-electron microscopy revealed GH immunoreactivity only. The lack of morphologic similarity between the 2 adenomas indicates that pituitary tumors in patients with Carney complex may not exhibit the same phenotype.     

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.     

The Spectrum of Pediatric Tumors in Infancy, Childhood, and Adolescence: A Comprehensive Review with Emphasis on Special Techniques in Diagnosis

The spectrum of pediatric tumors varies considerably, from those derived from blastemal cells in various organ systems to proliferations of soft tissue supporting cells to hamartomatous processes that mimic malignant tumors. Small round cell tumors are often undifferentiated or poorly differentiated, making it difficult sometimes to provide a definitive diagnosis. Both benign and malignant tumors require a coordinated method for diagnosis, and need a comprehensive evaluation to provide the most appropriate diagnosis for designing therapy and predicting prognosis. Pediatric tumors require the integration of routine histopathologic examination with histochemical, immunocytochemical, ultrastructural, cytogenetic, and diagnostic molecular pathology techniques. This review provides updated guidelines with respect to the application of these special techniques in this rapidly evolving diagnostic arena.     

The Spectrum of Pediatric Tumors in Infancy,Childhood, and Adolescence: A Comprehensive Review with Emphasis on Special Techniques in Diagnosis

The spectrum of pediatric tumors varies considerably, from those derived from blastemal cells in various organ systems to proliferations of soft tissue supporting cells to hamartomatous processes that mimic malignant tumors. Small round cell tumors are often undifferentiated or poorly differentiated, making it difficult sometimes to provide a definitive diagnosis. Both benign and malignant tumors require a coordinated method for diagnosis, and need a comprehensive evaluation to provide the most appropriate diagnosis for designing therapy and predicting prognosis. Pediatric tumors require the integration of routine histopathologic examination with histochemical, immunocytochemical, ultrastructural, cytogenetic, and diagnostic molecular pathology techniques. This review provides updated guidelines with respect to the application of these special techniques in this rapidly evolving diagnostic arena.