Pathology of Atretic Encephaloceles in Children

Pathogenesis

• Unclear pathogenesis – mesodermal insufficiency vs. blowout: Theories about atretic encephalocele development include (a) a primary mesodermal insufficiency or (b) a blowout phenomenon leading to herniation of intracranial contents through a small skull bone defect that subsequently undergo involution (21, 28). Genetic or environmental insults to the multipotential primary mesenchyme interposed between the neural tube and the superficial one-layered ectoderm may give rise to the development of an atretic encephalocele.
• Non-repair of defect in epithelium second month in utero: In 1932, Ingalls described frequent defects in the dorsal coverings of the embryo, in the form of blebs, blisters, loss of superficial epithelium, hyperpigmentation, overgrowths, and connective tissue thickening, all at about 2 months of fetal age (10). Ingalls stressed the high frequency of these lesions in embryos in contrast with their rarity in the fully developed infant, suggesting that most lesions undergo a spontaneous repair process (10). Atretic encephaloceles might represent the persistence of these blebs that Inoue et al. designated as “remnant nuchal bleb” (11).
• Anomalous fissure formation during second month of gestation: In 1973, Ruano and Domenech (27), reporting on the development of the human leptomeninges, documented an anomalous fissure between the dorsal aspect of the mesencephalon and the embryo surface with everted margins, dating the origin of this anomaly to Streeter’s stage XXIII (gestation day 47).
• Relationship to sagittal sinus development: Patterson et al. related atretic encephaloceles to the development of the sagittal venous system and state that atretic encephaloceles must originate before 10-week gestation age (26).
• 1–3 cm diameter abnormal skin with underlying skull defect: Macroscopically, atretic encephaloceles may appear as cystic or solid subscalp masses ranging from 1–3 cm in diameter (21, 28). The lesion may be alopecic or covered by normal hair or surrounded by abnormally long hair (“the collar sign”). The skin may be thinned, angiomatous, or resemble a congenital scar. Atretic encephaloceles may be hard, may collapse on expression, or may even engorge after straining depending on the contents. Exceptionally, an atretic encephalocele may leak fluid. On palpation, there is an underlying skull defect, which distinguishes atretic encephaloceles from subscalp nodules of heterotopic or ectopic tissues (21, 23). 
• Skull defect differentiates from other scalp anomalies: Briefly, atretic encephaloceles consist of (a) herniation of intracranial tissues of diverse nature, and (b) an underlying skull defect (21). Lesions without a bone defect are best grouped into ectopic or heterotopic neuroglial or meningeal rests (21, 23).

Molecular/Genetic Pathology

• Autosomal recessive and autosomal dominant inheritance reported: Most cases of atretic encephalocele are sporadic. However, instances with familial presentation have been reported (19). An autosomal dominant or autosomal recessive inheritance pattern has been suggested for these cases (5, 12, 19, 31, 34). A genetic linkage has been found in several syndromes, as in Walker-Warburg syndrome, autosomal dominant Dandy-Walker malformation with occipital encephaloceles, and Zechi-Ceide syndrome (5, 12, 31, 34).
• Inductive influences of the neural tube play an uncertain role: Atretic encephaloceles may (a) present as an isolated condition, (b) be associated with diverse CNS malformations, or (c) form part of a severe syndrome (16, 21, 28).

Histopathology

• Stalk, neuroglia, and vessels: Atretic encephaloceles are composed of neuroglial elements, fetal blood vessels and a fibrous connective stalk (16). Exceptionally, there may be ependymal cells lining the cavity in cystic lesions (3). Atretic encephaloceles may also have a lipomatous component connecting the subscalp mass with the mesencephalic cisterns (1).

Categorization

In the author’s view, the heterogeneous composition of atretic encephaloceles represents a continuum that illustrates the diverse stages in the development of these lesions (16). The lesions have been classified according to their composition:

• With or without skull defect: Drapkin (9) classified atretic encephaloceles into two varieties. Type A lacks an intracranial connection, and type B presents with a skull defect.
• Presence or absence of neuroglial tissue: Martínez-Lage et al. reported two varieties of atretic encephalocele (16). Type 1 consists of arachnoid tissue at the fibrous stalk plus a cluster of fetal vessels with normal dermal hair follicles at the lesion’s dome. Type 2 consists of meninges intermingled with dermal fibrous tissue, anomalous vessels and ectopic foci of neural and/or glial tissue. In older patients, the lesions may undergo regression and become firmer containing more meningeal and fibrous elements.