Background

Desmoplastic astrocytomas (DAs) are uncommon tumors which usually involve the superficial cerebral cortex and meninges of the supratentorial compartment in pediatric patients. These neoplasms were first described in 1982 by Taratuto et al. [33] and are currently considered as a grade I neoplasm by the World Health Organization (WHO). Microscopically, DAs consist of three distinct elements [15, 33]. The desmoplastic leptomeningeal component contains a mixture of fibroblast-like spindle-shaped cells and pleomorphic neoplastic neuroepithelial cells with eosinophilic cytoplasm, both arranged in fascicles or in a storiform pattern and embedded in a prominent reticulin network [15, 33]. The immature component consists of poorly differentiated neuroepithelial cells [15, 33]. Most of the tumor remains in the subarachnoid space respecting the pial layer, but tongues of neoplastic tissue extend into the leptomeninges, Virchow-Robin spaces, and the adjacent cortex (cortical component), producing a vigorous reactive astrocytosis [15, 33].

Given the dearth of large series in the scientific literature, the diagnostic and therapeutic management of DAs have not been well established and are mainly based on the limited knowledge obtained from the study of case reports. In this revision, we present two new patients diagnosed of DA and include a thorough review of similar cases reported on since the first description of this entity to date.

Material and methods

A systematic review of the literature was carried out in the Pubmed database using the terms desmoplastic and astrocytoma. A total of 106 references were obtained, and only those papers reporting cases of pathologically verified DAs were selected. Additional cases were gathered from the study of their references lists. Data concerning the epidemiology, clinical and radiological features, pathological findings, therapy, and follow-up of the patients were collected. Two new cases were identified among the oncological records of our institution and were included in order to illustrate this review. Descriptive and analytic statistics were accomplished by using the SPSS software (version 20).

Results

Demography

A total of 52 cases were gathered (Table 1). Their age (n = 52) ranged from newborn to 18 years old (mean 25.4 months, median 7 months) (Fig. 1). Males were 56.3 % (n = 48). The most common clinical symptoms (n = 49) occurred as a result of elevated intracranial pressure (42.9 %). Of patients, 16.3 % presented focal symptoms, including hemiparesis (13 cases), cranial nerve deficit (2 cases), visual field deficit (6 cases), nystagmus (3 cases), and paraparesis (2 cases). Seizures were recorded in 6.1 % of cases. About a third of the patients presented a variable combination of the three main categories of symptoms enumerated above. Only one case of DA was diagnosed incidentally, after suffering a cranial traumatism, but a visual field deficit was subsequently revealed [30]. The onset of clinical symptoms was either acute (up to 1 day) (11.4 %), subacute (up to 1 month) (50 %), or chronic (36.4 %). In one case, symptoms were present at delivery [33]. Association of DA with a congenital syndrome occurred only in one patient [16].

Table 1 Cases of DA reported on in the literature
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Fig. 1
figure 1

Graph illustrating dispersion of the variable age, measured in months, among the 52 cases of DA

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Diagnosis

Radiological diagnosis (n = 49) was based on CT (40.8 %), MRI (32.7 %), or both (24.5 %). One case was diagnosed by employing echography and MRI (case 52). On the basis of their neuroradiological features, we were able to classify DAs in four main categories as follows. Type 1 DAs (67.3 %) are predominantly cystic tumors with a superficial, mural, contrast-enhancing solid component. The cyst is characteristically deep-seated, multiloculated, and bigger than the nodular component. Its content displays a signal similar to cerebrospinal fluid. Enhancement of the cyst wall is extraordinarily rare [3, 5]. Type 2 includes those solid DAs with a hypodense (hypointense on T1-weighted MRI) center and ring enhancement (5.8 %). Solid DAs with homogeneous enhancement were classified as type 3 (15.4 %). These tumors often contained small cystic areas. Type 4 groups together those cases displaying multiple lesions in the central nervous system at the moment of diagnosis (11.5 %).

Tumors presenting as a unique lesion (types 1 to 3) (n = 46) were mostly located in the supratentorial compartment (95 %), with a similar distribution between hemispheres. The size of these lesions (n = 39) ranged from 2.5 to 13 cm (mean 8.4, median 8.25), so three quarters of these unique, supratentorial DAs involved at least two cerebral lobes, especially the frontal and parietal areas. Exceptionally, suprasellar [38] and spinal [25] single DAs were also reported.

Single tumors typically presented a close relationship with a dural surface, mostly at the convexity (29 cases) but also at the parasagittal area (6 cases), the falco-tentorial junction (2 cases), the tentorium (2 cases), or the central middle cranial base (1 case). Duramater and arachnoid thickening with enhancement was present in 40.6 % of these tumors (n = 32). Vasogenic edema (n = 32) could only be identified in 13 cases and was usually from mild to moderate. Significant mass effect with brain shift (n = 38) was evident in 94.7 % of single tumors and was especially associated with type 1 DAs (28 cases).

Six patients presented multiple neoplastic lesions (type 4). Four of them displayed high-sized lesions in the suprasellar area [1, 6, 8, 31]. One patient developed bilateral supratentorial lesions [29], and in one case, a mesial temporal mass extending to the interpeduncular cistern was described [37]. Additional tumoral lesions were mainly identified in the posterior fossa (five cases) [1, 8, 29, 31, 37] and along the spinal axis (three cases) [1, 28, 31]. Malignant cells were evidenced by cytological analysis of cerebrospinal fluid in one case [31].

Radiological signs of active hydrocephalus were present in 15 cases. An obstructive mechanism caused by severe midline displacement [3, 10, 12, 19, 20, 23, 26, 32, 33, 35, 38] or a large suprasellar mass [8] was implied in 12 of them. Communicant hydrocephalus was diagnosed in one patient [29], and a mixed mechanism was involved in two cases [6, 31]. Only four patients required a ventricular-peritoneal shunt.

Calcifications were described in five tumors [14, 21, 24, 29, 34, 37]. Involvement of the cranium was rarely present and consisted in cranial bossing [7, 10, 20, 32–34] or erosion [23, 28, 33].

Angiography was performed in six cases; DAs were mainly described as avascular masses [13, 18, 24, 33], although tumoral blush with vascularization from pial feeders was also described in two cases [5, 20].

Surgical treatment

Surgical features of DAs were thoroughly described in 42 cases. Most common findings among type 1 DAs (26 cases) included a solid, superficial, firm rubbery component that could be grayish, ivory-colored, or purplish. It was typically avascular and presented tight adhesions to the duramater, occasionally eroding the bone [28], and finger-like projections that seemed to blend with the adjacent cortex. In one case, this solid component displayed a deeper location and was attached to an intracystic septum [24]. The deep-seated cystic component always contained clear or xanthocromic fluid, but in one DA, the presence of dark fluid was attributed to hemorrhage [3].

Surgical findings in type 2 (n = 2) and 3 (n = 6) tumors resembled those of the solid component of type 1 DAs, with one report describing signs of old and recent intratumoral hemorrhage [13].

Removal degree of single lesions (types 1–3) was described as total in 65.2 %, subtotal in 19.6 %, and partial in 13 % of cases. Only one tumor was biopsied [20]. Among the causes precluding a complete resection, the following were listed: tight adhesion to a major venous sinus (four cases), absence of plane of dissection with the surrounding brain (four cases), massive blood loss (two cases), eloquent parenchyma involvement (one case), and avoidance of brain collapse putting bridging veins under excessive tension (one case) [35].

Multiple lesions (type 4 DAs) were managed by biopsy (two cases) or complete resection of the most accessible or symptomatic mass (two cases). Setty et al. [31] performed a biopsy of a suprasellar lesion and observed opacification and thickening of the leptomeninges of the basal cisterns, which were attributed to leptomeningeal spread of the tumor. Darwish et al. [8] attempted to remove a giant suprasellar mass, but it was precluded by encasement of the internal carotid artery. Finally, Santosh et al. [29] performed a palliative procedure with resection of a right frontal mass and punction of a contralateral cystic lesion.

Puncture of the cyst was also carried out in six single DAs. This procedure was performed through the anterior fontanelle or a burr hole to alleviate acute intracranial hypertension [10, 11] or during elective surgery in order to relax the underlying brain [4, 5, 32].

Eight patients developed surgical complications (n = 52), which included respiratory failure [33], massive blood loss [20, 34], arterial infarction [2], subdural higroma (case 52) [2], worsening of neurological deficit [37], and hydrocephalus [2].

Pathology

All tumors fulfilled the WHO criteria described above for the diagnosis of DA. Nevertheless, six tumors presented aggressive focal signs such as an increased mitotic rate, necrosis, or both (Table 1). A detailed microscopical analysis of the cyst wall in type 1 DAs showed cerebral atrophy with normal layered architecture, with intense gliosis in the outer layers and interstitial edema in the innermost part of the cyst wall [11]. There were no records of tumor invasion of the cyst wall, even in those cases which displayed contrast enhancement [5].

Adjuvant treatment

Fourteen patients received adjuvant treatment including chemotherapy (Cht), radiotherapy (Rt), or both (Table 1). Cht drug regimens were variable and included combinations of vincristine, carboplatin, methotrexate, and cisplatin [3]; carboplatin, ifosfamide, etoposide, and vincristine [31]; vincristine, cyclophosphamide, methotrexate, carboplatin, and etoposide [6]; and vincristine and carboplatin [37]. An aggressive Cht regimen was the cause of severe neurological impairment in one patient [31].

Details of Rt were not provided in most cases. Taratuto et al. [33] treated their patients with conventional Rt including 3500 to 5000 rad, and 30 cycles of 1.8 Gy were applied by Kopniczky et al. [16] to the tumoral bed in their case. Rt and Cht were also employed in the setting of progression or recurrence of the disease as described below.

Outcome

Follow-up was reported in 45 cases and ranged from 2 to 150 months (mean 34.6). Local recurrence of the tumor after gross total resection was detected in three patients [2, 12, 24], and progression of the disease was reported in five cases [6, 8, 20, 22, 34]. Progression and recurrence were treated as described in Table 1. The case published by Abuharbid et al. [1] experienced progression of some lesions, while others spontaneously regressed. Tumoral regression was also reported in a case of type 1 DA treated by subtotal resection [35].

The final clinical status of the patients was described in 49 cases. Most of them (75.5 %) progressed normally, but 14.2 % presented a neurological deficit, which was considered as disabling in six patients at last follow-up examination. Five patients (10.2 %) died as a consequence of surgical complications [20, 33] or progression of the disease [6, 8, 34]. Mortality rates affected especially those patients diagnosed of type 4 (33.3 %) and type 3 (28.6 %) DAs. An analysis of the outcome, comparing those patients who followed a good clinical course (normal development or mild neurological deficit) with those who experienced a poorer one (severe neurological deficit or death), demonstrated a statistical significant difference between type 1 and the remaining DA types (Fisher’s exact test, p = 0.001). A poor prognosis was also associated with the presence of recurrence or progression of the neoplasm (p = 0.009), but there was no relationship with the diagnosis of microscopic aggressive signs (p = 0.605).

Illustrative cases

Case 1

A 5-month-old male presented facial asymmetry and progressive pathological enlargement of the occipitofrontal circumference. Brain MRI demonstrated a left fronto-parietal mass (Fig. 2a–c). A subtotal resection of the tumor was carried out (Fig. 2d–e), except for a small portion of 1 cm tightly adherent to the superior sagital sinus. The fluid drained from the cystic component was acellular, and the pathological findings were consistent with the diagnosis of DA. The patient remains asymptomatic 4 years after the surgical procedure, and last follow-up MRI showed stability of the small tumoral remnant (Fig. 2f).

Fig. 2
figure 2

Preoperative brain MRI corresponding to case 1 (a–c). a T1WI, sagittal slice showing a 9 × 6 × 5.5 cm solid cystic tumor in the left frontal and parietal lobes. The solid portion displays an isointense signal, while that corresponding to the cyst contents is hypointense. b Strong, homogeneous enhancement of the solid component after administration of gadolinium. c T2-weighted MRI, axial slice showing the isointense signal of the solid component and hyperintense signal in the cyst. The tumor associates with moderate vasogenic edema. d Intraoperative findings consisting in tight adherence of the solid component of the tumor (t) to the convexity duramater (d), that was dissected with bipolar coagulation (transparent arrow). This solid component seemed to blend with the adjacent brain (small arrows) and becomes translucent, insinuating the underlying cyst. A plane of consistence was used for dissection. e Final stages of the surgical procedure, showing the falx cerebri (f) and a portion of the tumor tightly adhered to the lateral wall of the sagittal sinus. Observe the collapse of the brain, which puts the bridging veins under tension (asterisk). f Postoperative T1-weighted, gadolinium-enhanced MRI, coronal slice showing a small remnant of the tumor in close relationship with the sagittal sinus

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Case 2

A 9-month-old female was admitted to our department with acute refractory vomiting. She had a history of progressive weakness of the left limbs and cranial enlargement during the last 2 months. Transfontanelar ultrasonography showed a giant multiloculated cystic lesion. Brain MRI demonstrated a mixed solid cystic lesion of 10 × 7 × 7 cm located in the right frontoparietal area. The solid region showed homogeneous enhancement after gadolinium administration. The tumor was completely removed through a right frontoparietal approach. She progressively recovered a normal motor function but presented a right frontal hygroma which resolved spontaneously over several months. Microscopical analysis of the lesion showed the typical features of DA (Fig. 3). Last follow-up MRI, performed 54 months after surgical treatment, showed no signs of recurrence of the tumor.

Fig. 3
figure 3

Microscopic pathological findings corresponding to case 2. a–b H-E x. Microscopically, the lesion consisted in astrocyte proliferation with intense desmoplasia, fascicular pattern of collagen, and reticulin fibers, with no evidence of necrosis, mitosis, or ganglion cells (a HE ×25 and b HE ×100). Tumoral cells were positive for GFAP immunostaining (c) (×100). Low positivity rate for Ki-67 (1 %) (d)

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Discussion

DAs must be considered rare neoplasms, with only 52 cases described to date. These tumors represented 1.25 % of all intracranial neoplasms of infancy and childhood in the series of Taratuto et al. [33], which included 483 patients over a 12-year period. In our experience, DAs comprised 2.9 % of brain tumors diagnosed in pediatric patients.

Most DAs were diagnosed in children aged less than 2 years old (Fig. 1), as were our own cases described above, suggesting a congenital development of the neoplasm. The large size of the tumors at diagnosis and the high frequency of acute and subacute clinical symptoms at presentation could traduce a relatively high rate of tumoral enlargement. However, DAs have also been described in older individuals, including the period of adolescence. Noteworthy, none of those patients diagnosed after the first 2 years of life was diagnosed of a type 1 DA. Some of this older patients presented neurological symptoms early after birth, but the cause was not investigated or was misdiagnosed [7, 18, 20], which led to severe neurological deficits as a consequence of progression of the disease [18]. Nevertheless, most of these older patients did not present previous medical records, suggesting that DAs can also develop during childhood [13, 16, 34, 36, 37] or adolescence [25].

The most common clinical symptoms in children aged less than 2 years old consisted of elevated intracranial pressure, including increased occipitofrontal circumference, feeding problems, bulging fontanelles, “sunset” eyes, vomiting, and impaired consciousness in severe cases. Older patients tended to present seizures and focal symptoms. DAs were not systematically associated with any congenital syndrome [16].

The term DA seems to encompass a more heterogeneous group of neoplasms than thought before. On the basis of their radiological appearance, we were able to classify these tumors in four main groups. Single lesions comprise types 1 to 3. Type 1, which should also be named as classic or typical DA, is characterized by the morphology described by Taratuto et al. [33] in their pioneering publication. The radiological differential diagnosis includes dysembryoplastic neuroepithelial tumor, pleomorphic xanthoastrocytoma, supratentorial ependymoma, ganglioglioma, and teratoma. The radiological differential diagnosis becomes more difficult in the absence of typical signs, so that type 2 tumors can be misdiagnosed as other more common ring-enhancing lesions. Type 3 DAs must be radiologically distinguished from other solid, contrast-enhancing lesions such as meningiomas and gliofibromas.

The treatment of choice of single DAs is complete tumor resection. But, these tumors often represent a surgical challenge as a consequence of their large size at diagnosis and their macroscopic morphology, which shares characteristics of both extra- and intra-axial tumors. The presence of tight attachments to extra-cerebral structures represents a special surgical issue to be addressed. Complete removal of the tumor becomes especially hazardous in those tumors intimately adhered to bridging veins, a dural sinus (Fig. 2d–e) or, more rarely, to major vessels and cranial nerves from the cranial base [2, 20, 34, 37]. As a matter of fact, the only fatal case reported among type 1 DAs was the consequence of a hypovolemic shock, which also occurred in one patient diagnosed of a type 3 neoplasm [20, 33]. Leaving a small remnant of the tumor adhered to these structures should be considered a valid strategy, given the generally benign biological behavior of these neoplasms.

Difficulties may also arise in those DAs located near eloquent cortex, as the tumoral mass presents extensions within the surrounding brain tissue (Fig. 2d). Nevertheless, a plane of consistence between the tumor and brain parenchyma, which coincides with the microscopic margin of the neoplasm, can usually be found and followed during dissection [32].

The brain tends to collapse after resection of these generally voluminous masses, putting the bridging veins under excessive tension and predisposing to the development of subdural effusions [10, 35]. These postoperative subdural hygromas must not be treated in the absence of clinical symptoms, as they tend to disappear over time, as occurred in one of our patients [10].

The cyst wall in type 1 DAs does not represent a true neoplastic component, so it should not be included in the resection plan [10, 11]. Moreover, the presence of a cyst is a clear advantage in the management of younger patients, allowing an initial diagnostic approach with transfontanellar ultrasound. This technique can guide a percutaneous or fontanellar puncture of the cyst, which becomes particularly useful in the setting of acute increased intracranial pressure [10, 11, 33]. This procedure can be repeated as needed to stabilize the patient during the diagnostic checkup [10]. During elective surgery, the cyst can also be evacuated before opening the duramater in order to avoid extensive brain herniation [4, 5, 32].

Needle biopsy should be avoided in those cases in which a radiological diagnosis of single DA has been performed. However, if biopsy is peremptory, it should be assured that a representative sample of the lesion is obtained. The results must also be interpreted with caution, as the mitotic activity is increased in the immature neoplastic component when compared to the desmoplastic one [20, 33], and a higher grade neoplasm may erroneously be diagnosed [20, 32].

Given their benign biological behavior, adjuvant therapy should not be systematically applied in single DAs. Even subtotal resections have been linked with a good prognosis, and spontaneous involution of tumoral remnants has also been reported [1, 35]. That said, all patients should be followed closely for early detection in case that local recurrence or progression of the tumor occur. These must be considered rare events, with only six cases described to date [2, 12, 20, 22, 24, 34], so we were not able to find an association with any variable, including the radiological type of single DA, the presence of microscopic aggressive features, and the degree of surgical removal of the neoplasm. In this context, most authors performed a second surgical procedure aimed at complete resection or cytoreduction, followed by chemotherapy and radiotherapy. Progression of the disease finally caused the death of one patient diagnosed of a type 3 DA [34].

Type 4 DAs deserve special consideration [27]. Most patients presented a large-sized solid tumor closely related to the basal cisterns and additional tumoral lesions along the neuraxis, suggesting a leptomeningeal dissemination of the disease [1, 6, 8, 31, 37]. This mechanism of spread was confirmed in one patient by cytological analysis of CSF [31] and was radiologically suspected in an additional case [6]. As an exception, the patient described by Santosh et al. developed multiple solid cystic lesions in the supratentorial compartment along several months, which could be attributed to metachronous disease. However, the presence of a reabsortive HCP in their patient can be interpreted as an indirect sign of leptomeningeal involvement [29].

Surgical management of type 4 DAs becomes restricted to biopsy or removal of an accessible and/or symptomatic lesion. Surgery was followed by chemotherapy in three cases [6, 31, 37], and control of the disease was achieved in two of them [31, 37]. All those patients who were not treated with chemotherapy experienced progression of the disease [1, 8], which finally caused one fatality [8]. Despite the obvious limitations of this series, it could be suggested that chemotherapy could play an important role in the management of multiple DAs, although this must be the object of future investigations [27].

Conclusions

  1. 1.

    DAs can be diagnosed in a wider range of age and appear with more variable radiological features than previously thought.

  2. 2.

    Our classification of DAs in four subgroups facilitates the radiological differential diagnosis and associates a prognostic value.

  3. 3.

    Gross total surgical resection is the treatment of choice of single DAs (types 1–3). This aim can be hampered by the specific macroscopic morphological features and location of the tumor.

  4. 4.

    Multiple lesions in DA type 4 seem to develop as a consequence of leptomeningeal dissemination. This type associates with a worse prognosis and subsequently requires a more aggressive therapeutic strategy.

  5. 5.

    Tumor recurrence must be considered a rare, unpredictable phenomenon, so close follow-up should be recommended in all patients. Recurrence should be treated by surgery and individualizing the decision of instauration of adjuvant treatment.