Heterotopia, or choristoma, is applied to aggregates of normally formed tissues that are present in aberrant anatomical locations. Examples of heterotopias include a patch of gastric mucosa in the upper third of the esophagus, a rest of pancreatic tissue in the gastrointestinal wall, or a parathyroid gland within the thymus in the anterior mediastium. Heterotopia is usually an incidental finding, but it can be confused clinically with a neoplasm. In exceptional cases, true neoplasms may arise from heterotopic tissues [8, 9].
Neuroglial heterotopia is a rare developmental anomaly with a rich variety of clinical features, pathological findings, and pathogenetic mechanisms. Based on anatomical location and pathological differentiation, Hori et al. proposed a classification of neuroglial heterotopia into extraneuraxial and paraneuraxial groups . Extraneuraxial neuroglial heterotopia is much more common and usually involves the nasal cavity or the superficial soft tissue of the head and neck. Pathologically, it is characterized by a disorganized mixture of neuroglial and mesenchymal tissues or a lump of organized neural tissue similar to normal brain histology. It is often obvious at birth but may remain asymptomatic until late childhood or even adulthood. Complete surgical excision is curative in most cases [1, 3, 10, 11]. On the other hand, paraneuraxial neuroglial heterotopia is rare and may involve the paracranial or paraspinal spaces, such as the occipital bone, retroperitoneum, and deep neck. It is composed of organized brain tissue and is usually diagnosed shortly after delivery or in early childhood. Disease-related complications are common [2, 6, 7, 12, 13].
The pathogenesis of neuroglial heterotopia is uncertain. Several pathogenetic hypotheses of extraneuraxial neuroglial heterotopia have been proposed, including (1) herniation of neuroectodermal tissue through a primary bony defect that is followed by a partial or complete secondary closure resulting in sequestration of the herniated tissue [1, 3]; (2) separation and detachment of cerebral precursors (which later mature ectopically) from the brain primordium in early embryogenesis [1, 12]; (3) aberrant migration of pluripotential embryonic tissue with subsequent neuroglial differentiation ; (4) retention of neuroectodermal remnants ; and (5) teratoma formation with a predominant or exclusive neuroglial component . However, no single hypothesis can completely explain all the varieties of extraneuraxial neuroglial heterotopia. In contrast, paraneuraxial neuroglial heterotopia is closely related to neural tube defects, such as encephalocele and myelomeningocele. For instance, paraneuraxial neuroglial heterotopia shares a similar anatomical distribution and histological features with encephalocele and myelomeningocele [2, 5–7, 12, 13]. A connection between the heterotopic neuroglial tissue and the intervertebral region via a string of connective tissue is found in some cases, and this gross picture is not much different from that of a myelomeningocele with an obliterated connection to the spinal cord [2, 6]. Accordingly, the “herniation and sequestration” hypothesis seems tenable to explain the pathogenesis of paraneuraxial neuroglial heterotopia. The process of “herniation and sequestration” acts like a mild or “partially corrected” version of neural tube defects. This is probably why concomitant congenital anomaly is far less frequent in paraneuraxial neuroglial heterotopia than in encephalocele and myelomeningocele.
In this report, we present a case of multifocal paraneuraxial, paraspinal neuroglial heterotopia concomitant with congenital anomalies associated with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. MRKH syndrome is regarded as an inhibitory malformation of the Müllerian ducts. It is characterized by agenesis of the uterus and the upper two-thirds of the vagina in individuals with a normal female karyotype [15, 16]. Associated anomalies of the renal, skeletal and cardiovascular systems are present in about half of cases, and this severe form of the disease is categorized as atypical MRKH or MURCS association [15, 16]. Ovarian agenesis, imperforated anus, polydactyly, and encephalocele have also been reported [15–18]. Although the pathogenesis of MRKH syndrome remains unclear, it is suggested that the spectrum of anomalies are attributed to the extent of developmental field defects that primarily affect the fetal mesoderm or its progenitor tissue in early embryogenesis . When such mesodermal defects involve the paraaxial mesoderm, encephalocele, myelomeningocele and paraneuraxial neuroglial heterotopia may develop [1, 3, 19]. Given the similarity of the pathogenetic hypotheses for paraspinal neuroglial heterotopia and Müllerian agenesis, we suggest that the present case constitutes an unusual variant of MRKH syndrome.