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Table of Contents    
Year : 2021  |  Volume : 69  |  Issue : 5  |  Page : 1204-1209

Prevalence and Pattern of Leptomeningeal Pigmentation in the Human Brain and Its Role in the Safe Surgical Excision of Extra-Axial Brain Tumors

1 Section of Neurosurgery, Department of Neurological Sciences, Christian Medical College Hospital, Vellore, Tamil Nadu, India
2 Pathology, Department of Neurological Sciences, Christian Medical College Hospital, Vellore, Tamil Nadu, India

Date of Submission17-Dec-2019
Date of Decision02-May-2020
Date of Acceptance16-Mar-2021
Date of Web Publication30-Oct-2021

Correspondence Address:
Ari G Chacko
Department of Neurological Sciences, Christian Medical College, Vellore, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.329529

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 » Abstract 

Background: Although leptomeningeal melanin pigmentation is well-known, it is not described in the neurosurgical literature. Dark pigmentation native to these transparent membranes might have microsurgical relevance in identifying a plane of dissection.
Objective: To describe the prevalence of leptomeningeal pigmentation and determine whether its recognition helps during microsurgical excision of extra-axial brain tumors.
Materials and Methods: This was a prospective cross-sectional observational study in cadavers and neurosurgical patients. Eight adult cadaveric brains were examined for leptomeningeal pigmentation and biopsies taken for histological studies. A total of 126 patients undergoing surgery for cerebellopontine angle and suprasellar lesions were included in the clinical study. The surgeon determined whether the recognition of pigmentation was useful during microneurosurgical arachnoid dissection.
Results: Seven of 8 cadavers (87.5%) had leptomeningeal pigmentation on the ventral pons, optic chiasm, lamina terminalis, olfactory tract, and gyrus rectus and infrequently on the cerebral convexities. The prevalence of pigmentation was 76.9% in the clinical study, was seen in all pediatric patients, and was significantly higher in males (P = 0.009), with no significant association with skin color. Immunochemistry identified the pigmentation as melanin. Recognition of this pigmentation was deemed to be useful during tumor excision in 78% of the cases.
Conclusions: Leptomeningeal melanin pigmentation has a prevalence of 76% to 87% in the Indian population and is more often seen in younger males. It is most commonly identified overlying the ventral brain stem and optic chiasm. Recognition of its presence is helpful during arachnoid dissection during most cerebellopontine angle and suprasellar tumor resections.

Keywords: Arachnoid, extra-axial, leptomeningeal, melanin, microneurosurgery, pigmentation
Key Messages: Leptomeningeal melanin pigmentation is highly prevalent in Indians and is commonly identified overlying the ventral brain stem and optic chiasm. Its recognition provides an additional landmark during arachnoid dissection of extra-axial tumors, particularly in the suprasellar and cerebellopontine angle cisterns.

How to cite this article:
Gupta A, Chacko G, Chacko AG. Prevalence and Pattern of Leptomeningeal Pigmentation in the Human Brain and Its Role in the Safe Surgical Excision of Extra-Axial Brain Tumors. Neurol India 2021;69:1204-9

How to cite this URL:
Gupta A, Chacko G, Chacko AG. Prevalence and Pattern of Leptomeningeal Pigmentation in the Human Brain and Its Role in the Safe Surgical Excision of Extra-Axial Brain Tumors. Neurol India [serial online] 2021 [cited 2022 May 25];69:1204-9. Available from: https://www.neurologyindia.com/text.asp?2021/69/5/1204/329529

Leptomeningeal pigmentation, although noted in 1824 by Ollivier d'Angers,[1] was first described in detail by Symmers[2] in 1905. The black pigmentation, discovered to be melanin, covers the spinal cord, brain stem, optic chiasm, and the orbitofrontal cerebral convolutions and seems to have no racial predilection, although reports are conflicting.[3],[4] During the excision of extra-axial tumors, the surgeon dissects the transparent arachnoid and pia mater off the tumor and may occasionally have difficulty in recognizing the arachnoid, leading to an unwanted breach of pia mater and neural tissue. Recognition of this leptomeningeal pigmentation may provide the surgeon with additional useful information thereby enabling a safe excision of the tumor. To our knowledge, no operative neurosurgery textbook mentions leptomeningeal pigmentation; therefore, we studied its prevalence among people of the Indian subcontinent and determined whether recognition of this leptomeningeal pigmentation during microsurgical excision of extra-axial brain lesions was useful.

 » Materials and Methods Top

This prospective cross-sectional, observational, clinical, and cadaveric study was initiated in 2012 after obtaining approval from the institutional review board (IRB No. 7786). It was conducted in the Department of Neurological Sciences in collaboration with the Section of Neuropathology and Department of Anatomy, within a tertiary care referral center in South India.

Cadaveric study design

We harvested brains from human cadavers that were received within 12 hours of death. The study design was in accordance with the QUACS (Quality Appraisal for Cadaveric Studies) scale.[5] We performed a detailed survey of each brain under the operating microscope (Zeiss Universal S3B) to look for pigmentation. For histological analysis, we obtained 1-cm2-sized leptomeningeal samples from the optic apparatus and 2-cm2-sized samples from the ventral pons, irrespective of whether pigmentation was seen under the operating microscope or not.

Clinical study design

Patient recruitment

Consecutive patients with extra-axial brain lesions in the suprasellar and cerebellopontine angles, in whom the optic apparatus, hypothalamus, brain stem, or the cerebellum would be seen during routine surgical resection of these lesions, were included. Informed consent was obtained prior to surgery; patients with intra-axial lesions were excluded from this study. Based on the senior author's prior surgical experience, we had seen this pigmentation in approximately 75% to 80% of our patients in the brain as well as on the spinal cord. To estimate the prevalence of leptomeningeal pigmentation with a precision of 7% to 9% and a confidence interval (CI) of 95%, the sample size calculated was 126.

Preoperative patient variables

Patients' demographic details such as age, sex, state of origin within India, and whether they had undergone any prior surgery or radiotherapy were noted. Skin color, usually in an area not exposed to the sun, such as under the arm, was graded according to the Von Luschan's[6] chromatic scale, consisting of 36 shades. We had used a simplified modification of this chromatic scale, as shown in [Table 1].
Table 1: The Von Luschan[6] chromatic scale that was used for grading of skin color. Our simplified skin color grading is depicted in the third column

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Intraoperative variables

Intraoperatively, we noted the presence and location of pigmentation with particular reference to its relationship to the tumor surface, brain, cranial nerves, and blood vessels. Structures were examined only if they were within the line of approach of the lesion. We also documented whether the recognition of this leptomeningeal pigmentation was useful in the identification of a neural structure as distinct from the tumor or in determining the plane of dissection. Intraoperative photographs of the pigmentation were taken directly from the microscope. In those cases where leptomeningeal pigmentation was identified, we subjectively classified the density of pigmentation as follows: Minimal: Only a few specks of pigmentation seen restricted to one focal region within a neural structure [Figure 1]a; Moderate: Pigmentation seen in discrete clusters, spread over multiple regions within a neural structure [Figure 1]b; Extensive: Widespread contiguous region of the neural structure carpeted with pigmentation [Figure 1]c.
Figure 1: Subjective grading of the density of leptomeningeal pigmentation, as seen under the operating microscope. (a) Minimal pigmentation seen over the optic chiasm (black arrow). (b) Moderate pigmentation (black arrows) over the brain stem, seen as multiple discrete clusters of pigmentation. (c) Extensive pigmentation seen as a carpet of dots spread over the entire optic chiasm

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Histopathological analysis

A small region of the pigmented pia/arachnoid was biopsied and sent for histopathological examination if deemed safe by the senior surgeon. All biopsies were fixed in buffered formalin for 6 to 12 hours. At least one section each was cut, for staining with hematoxylin and eosin (H and E) and for melanin bleach. On H and E staining, we looked for brownish stained granules located within leptomeningeal tissue that could represent melanin or hemosiderin. With the melanin bleach, the brown staining of melanin granules would be lost, whereas it would be retained if it was hemosiderin. Immunohistochemistry was then performed on all cases using the Melan-A antibody on the Ventana BenchMark XT autostainer. On the Melan-A immunohistochemistry, a distinct brown stain scattered over the leptomeninges, conforming to the pattern seen on the H and E-stained slides confirmed the presence of melanin pigment within the melanocytes.

Data analysis

Data were entered into a Microsoft Access 2007 database, and the analysis was performed after exporting the data into SPSS Statistics (IBM Version 20). Normative data were presented in terms of mean and standard deviation. The results of Chi-square tests were considered significant if the P value was less than 0.05. The results of logistic regression analysis were denoted in terms of odds ratio (OR), CI, and P value.

 » Results Top

Cadaveric study

The eight cadaveric specimens, including seven males, had a mean age of 48 years, ranging from 19 to 72 years. The commonest site of pigmentation (n = 6, 75%) was the brain stem, on the ventral surface of the pons [Table 2] and [Figure 2]. Leptomeningeal pigmentation was identified in seven of the eight cadavers – a prevalence of 87.5%, and this pigmentation was confirmed to be melanin on H and E and immunohistochemistry. In Cadaver 2, although no pigmentation was seen over the optic chiasm through the operating microscope, melanin pigmentation was identified at histology and confirmed on the Melan-A stains. The melanin pigment within the dendritic leptomeningeal cells had one of two patterns – a branching, reticulate pattern or a serpiginous pattern [Figure 3] and [Figure 4].
Figure 2: Leptomeningeal pigmentation seen over the ventral pons in a cadaveric brain. (a) Specks of pigmentation over the ventral pons near the midline (black arrows) and over the optic chiasm (arrow head). (b) Diffuse leptomeningeal pigmentation spread over the entire ventral surface of pons in another cadaver

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Figure 3: Histological photograph of leptomeningeal tissue over the brain stem in a cadaveric specimen. (a) Hematoxylin and eosin–stained tissue viewed at 200 × magnification, showing scattered brownish granules within the leptomeningeal cells (black arrows). (b) The same specimen viewed under 200 × magnification with Melan-A staining shows bleaching of the leptomeningeal tissue and the presence of brownish melanin granules within the tissue (black arrows)

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Figure 4: Leptomeningeal tissue obtained from the optic chiasm of a cadaveric specimen, when viewed under 1,000 × magnification. (a) Hematoxylin and eosin staining shows serpiginous clusters of brownish pigmented cells (black arrows). (b) On Melan-A immunohistochemistry, the pigment stains dense brown in color (black arrows) over a blue background

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Table 2: Description of the sites and density of leptomeningeal pigmentation in the cadaveric brain specimens, as examined under the operating microscope

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Clinical study

Patient demographics

A total of 126 patients were included in the clinical component of the study. There was a male predominance in our cohort, with 72 (57.1%) of the patients being males. The mean age of the cohort was 37.2 years ± 16 years, ranging from 4 to 73 years. Twenty-three patients (18.3%) had been previously operated and four had also undergone radiation therapy prior to our surgery: two with suprasellar craniopharyngiomas, one glossopharyngeal schwannoma, and the one patient had a vestibular schwannoma.

The majority of our patients were from West Bengal (27.8%, n = 35), followed by Bangladesh (17.5%, n = 22), Kerala (14.3%, n = 18), and Tamil Nadu (11%, n = 14). Other states of India contributed a few patients each. There were no Africans or Caucasians in the study.

Skin color

The majority of our patients were intermediate skin colored (n = 100, 78.7%), with only one light skin-colored patient, and the remaining 25 patients were dark skin colored. The mean skin color for our cohort was 23.08 ± 6.05, which fell in the intermediate skin color group.

Appearance of leptomeningeal pigmentation

Under the operating microscope at high zoom, we noticed two different patterns of leptomeningeal pigmentation. Over the optic chiasm [Figure 5]a and olfactory tract [Figure 5]b, the pigmentation was often seen as discrete rounded specks, tightly adherent to the neural structures in the intimal pial layer. On the brain stem [Figure 5]c and lamina terminalis [Figure 5]d, we frequently noticed a loosely arranged, branching, reticulate network-like pattern to the pigmentation in the epipial layer where the arachnoid could be safely elevated off the tumor.
Figure 5: Leptomeningeal pigmentation seen as discrete punctate dots tightly adherent to the intimal pial layer over the optic chiasm (a) and olfactory tract (b) in a patient with a suprasellar and third ventricular craniopharyngioma. (c) Clusters of branching reticulate leptomeningeal pigmentation (long arrow) seen at the tumor (small arrow)–brain stem interface. (d) Branching pial pigmentation seen over the lamina terminalis that is loosely adherent to the underlying neural structure and can be easily peeled off

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Prevalence of leptomeningeal pigmentation

The overall prevalence of leptomeningeal pigmentation in our cohort was 76.9%, as it was identified in 97 out of 126 patients. In these 97 patients, the density of pigmentation was extensive in 28 patients (28.9%), moderate in 58 patients (59.8%), and minimal in 11 patients (11.3%).

Age: The mean age of patients in whom the pigmentation was identified was 35.5 ± 17 years, as compared with those in whom it was absent (43.2 years ± 11.4 years). This difference in age was statistically significant (P = 0.021). Interestingly, all patients <18 years had leptomeningeal pigmentation.

Gender: Pigmentation was also found to be more prevalent in males as compared with females, seen in 86.3% of males as compared with 63% females, a difference that was statistically significant (P = 0.002).

Skin color: There was a higher prevalence of pigmentation in individuals with an intermediate skin color as compared with those with dark skin colors (78% and 69.3%, respectively), but this was not statistically significant (P = 0.350).

Pathology: The various pathologies in our cohort are listed in [Table 3]. When comparing the two most common pathologies studied, that is, craniopharyngiomas and vestibular schwannomas, there was a higher prevalence of leptomeningeal pigmentation associated with craniopharyngiomas (89.7%) as compared with vestibular schwannomas (74.1%), and this difference tended towards significance (OR = 3.062, 95% CI [0.922, 10.170], P = 0.068).
Table 3: Pathological diagnoses of the clinical cohort of patients (n=126)

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Location: The prevalence of pigmentation on various neural structures is listed in [Table 4].
Table 4: Prevalence of leptomeningeal pigmentation over various neural structures

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On doing a multivariate analysis [Table 5] to assess the association of age, gender, skin color, pathology, and location with the presence of leptomeningeal pigmentation, younger age and male gender continued to remain significant (P values 0.018 and 0.002, respectively).
Table 5: Multivariate analysis to assess association with leptomeningeal pigmentation in the entire cohort (n=126)

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Histopathological analysis

Leptomeningeal biopsy samples were obtained in 48 of 97 patients in whom the pigmentation could be identified (49.5%). Of the 48 samples, 41 samples were confirmed to have melanin pigment in melanocytes. In seven cases, no melanin could be identified either due to crush artifacts or inadequate tissue. H and E-stained sections showed a fine layer of leptomeningeal tissue containing spindle-shaped cells with dense intracytoplasmic brownish-black granular pigment obscuring other cytomorphological details. The cells were immunopositive for Melan-A.

Surgical implications of the leptomeningeal pigmentation

Recognition of the pigmentation was deemed to be useful; that is, it aided the surgeon in identifying the plane of arachnoid dissection to resect the tumor in 76 cases out of 97 (78.4%) in which the pigmentation was identified. Among these cases (n = 76), the plane of arachnoid dissection was found to be good in 70 cases (92.1%), moderate in five cases (6.6%), and poor in one case (1.3%) of a tuberculum sellae meningioma.

 » Discussion Top

Leptomeningeal pigmentation in humans

Leptomeningeal pigmentation has been described to be of neural crest melanocytic lineage.[7],[8],[9],[10],[11],[12],[13],[14] Symmers,[2] in 1905, noted a brown to black pigmentation covering the spinal cord, medulla, cerebral peduncles, and ventral surface of the brain, including the optic chiasm and the orbitofrontal cerebral cortex during routine postmortem examinations in Egypt. In a series of 200 postmortem examinations spanning 11 different racial types, the pigmentation was most marked in Egyptians who were light brown skinned. On the contrary, in 1969, a study from Uganda concluded that light-skinned Africans had little or no pigmentation in the leptomeninges, whereas darker skinned people showed more widespread pigmentation.[3] A qualitative and quantitative study in 15 Caucasian cadavers discovered melanin pigmentation limited to the leptomeninges overlying the ventrolateral aspect of the medulla oblongata.[4] The lack of magnification used in the study and limited sampling might explain the restricted distribution of the pigmentation.

Prevalence of leptomeningeal pigmentation in the Indian population

The prevalence of leptomeningeal pigmentation seems to range between 77% and 88% in the Indian population, most commonly on the ventral pons (particularly around the root entry zones of cranial nerves), followed by the optic chiasm, lamina terminalis, and olfactory tract. Our finding that the extent and density of pigmentation did not correlate with skin color needs to be interpreted with caution as the majority of our patients had an intermediate skin complexion. Broniatowsky, in 1911, noticed that pigment-laden branching cells first appeared by the ninth year of life, prior to which the spindle and branching cells lacked pigment.[15] However, in our cohort, we had nine children younger than nine years of age, each with a suprasellar craniopharyngioma, who had moderate to extensive leptomeningeal pigmentation seen over the optic apparatus. We found the pigmentation to be more prevalent in males and in the pediatric population on a logistic regression analysis, both findings that had not been reported earlier. The reasons for these differences remain unknown.

Surgical implications

We found that identification of the pigmentation was useful during surgical dissection, particularly at the root entry zones of the cranial nerves in cerebellopontine angle tumors and on the optic apparatus/hypothalamus in suprasellar tumors. One such clinical case is illustrated in [Figure 6].
Figure 6: (a) Intraoperative photograph during resection of a vestibular schwannoma, showing leptomeningeal pigmentation (black arrows) distributed along the entire tumor–brain stem interface. The pigmented pia/arachnoid extending onto the tumor surface was used as the plane of dissection. (b) Hematoxylin and eosin photomicrograph at 1,000 × magnification demonstrating the clusters of brownish melanin pigmentation (black arrow). (c) On Melan-A immunohistochemistry, the melanin-containing cells stain brown (black arrow) – 1,000 × magnification

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Identification of the tumor–arachnoid interface is of paramount importance during resection of tumors in the subarachnoid cisterns. Since the pia mater and arachnoid are translucent, identification of the appropriate plane of dissection can pose a challenge to the novice and expert alike, due to tight adherence of the tumor to the pia/arachnoid, tumor infiltration as in meningiomas, intraoperative bleeding, or incorrect plane of dissection. During these times, identification of this leptomeningeal pigmentation enables grasping the pia/arachnoid with a micro-bayonet and peeling it off the tumor toward the normal brain, adhering to the principle that “pigmentation belongs to the patient and not the tumor” [Video 1].


As there is no mention of leptomeningeal pigmentation in operative neurosurgery textbooks, we wondered whether this pigmentation was present at all in the Western population. However, our study does not answer this question as our patient population was restricted to South Asians alone. A broader study that includes Caucasians, Africans, American Indians, and East Asians might yield interesting results with regard to the prevalence of pigmentation in these races.

 » Conclusions Top

Leptomeningeal melanin pigmentation is seen in the majority of South Asians, particularly younger male patients. The recognition of this pigmentation provides an additional landmark during arachnoid–tumor dissection in the suprasellar and cerebellopontine angle cisterns, where the pigmentation is most frequently seen.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

This study was funded by the internal institutional grant (FLUID research grant) for postgraduate research activities, at the Christian Medical College, Vellore, Tamil Nadu, India.

Conflicts of interest

There are no conflicts of interest.

 » References Top

Flores-Sarnat L. Neurocutaneous melanocytosis. In: Handbook of Clinical Neurology - Paediatric Neurology Part 1. Amsterdam: Elsevier 2013; p. 369-91.  Back to cited text no. 1
Symmers WSC. Pigmentation of the pia mater, with special reference to the brain of modern Egyptians. J Anat Physiol 1905;40:25-7.  Back to cited text no. 2
Lewis MG. Melanoma and pigmentation of the leptomeninges in Ugandan Africans. J Clin Pathol 1969;22:183-6.  Back to cited text no. 3
Goldgeier MH, Klein LE, Klein-Angerer S, Moellmann G, Nordlund JJ. The distribution of melanocytes in the leptomeninges of the human brain. J Invest Dermatol 1984;82:235-8.  Back to cited text no. 4
Wilke J, Krause F, Niederer D, Engeroff T, Nürnberger F, Vogt L, et al. Appraising the methodological quality of cadaveric studies: Validation of the QUACS scale. J Anat 2015;226:440-6.  Back to cited text no. 5
Von Luschan E, Von Luschan F. Anthropologische messungen an 95 Englandern. Z Ethnol 1914;46:58-80.  Back to cited text no. 6
Barshes N, Demopoulos A, Engelhard HH. Anatomy and physiology of the leptomeninges and CSF space. Cancer Treat Res 2005;125:1-16.  Back to cited text no. 7
O'Rahilly R, Müller F. The meninges in human development. J Neuropathol Exp Neurol 1986;45:588-608.  Back to cited text no. 8
Agarwalla PK, Koch MJ, Mordes DA, Codd PJ, Coumans J-V. Pigmented lesions of the nervous system and the neural crest lessons from embryology. Neurosurgery 2016;78:142-55.  Back to cited text no. 9
Lim J, Thiery JP. Epithelial-mesenchymal transitions: Insights from development. Development 2012;139:3471-86.  Back to cited text no. 10
Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell 2009;139:871-90.  Back to cited text no. 11
Le Douarin NM, Dupin E. Multipotentiality of the neural crest. Curr Opin Genet Dev 2003;13:529-36.  Back to cited text no. 12
Theveneau E, Mayor R. Neural crest delamination and migration: From epithelium-to-mesenchyme transition to collective cell migration. Dev Biol 2012;366:34-54.  Back to cited text no. 13
Adameyko I, Lallemend F, Aquino JB, Pereira JA, Topilko P, Müller T, et al. Schwann cell precursors from nerve innervation are a cellular origin of melanocytes in skin. Cell 2009;139:366-79.  Back to cited text no. 14
MacLachlan WWG. Extensive pigmentation of the brain associated with nevi pigmentosi of the skin. J Med Res 1914;29:433-46.1.  Back to cited text no. 15


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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