Melanocytic colonization of choroid plexus papilloma: a previously undocumented source of pigment storage in the plexogenic epithelium

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Article

Reference

Melanocytic colonization of choroid plexus papilloma: a previously undocumented source of pigment storage in the plexogenic

epithelium

EGERVARI, Kristof Levente, et al .

EGERVARI, Kristof Levente, et al . Melanocytic colonization of choroid plexus papilloma: a previously undocumented source of pigment storage in the plexogenic epithelium. Clinical Neuropathology , 2019, vol. 38, no. 5, p. 249-252

DOI : 10.5414/NP301200 PMID : 31296285

Available at:

http://archive-ouverte.unige.ch/unige:122779

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Letter

e-pub: July 12, 2019

LETTER TO THE EDITOR Melanocytic colonization of choroid plexus papilloma:

A previously undocumented source of pigment storage in the plexogenic epithelium

Kristof Egervari^1,2, Johannes A.

Lobrinus^1,2, Doron Merkler^1,2, and Istvan Vajtai²

1Neuropathology Unit and ²Service of Clinical Pathology, Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland

Sir, – Primary central nervous system (CNS) tumors that are intrinsically defined as being melanized encompass less than a handful of entities (i.e., meningeal melano- cytoma and malignant melanoma, melanotic neuroectodermal tumor of infancy, melanotic psammomatous Schwannoma) [1].

Conversely, aberrant pigment production by tumor cells as a seemingly erratic secondary phenomenon has been documented in several unrelated CNS neoplasms. The better- known examples include pigmented variants of pilocytic astrocytoma [2], pleomorphic xanthoastrocytoma [3], ependymoma [4], ganglioglioma [5], dysembryoplastic neuroepithelial tumor [6], glioblastoma [7], medulloblastoma [8], and choroid plexus papilloma [9, 10, 11, 12].

From case to case, the intracellular pigment may be either of melanosomal origin [3, 5, 7, 8] or neuromelanin/lipofuscin [2, 11], and has variously been interpreted as re- flecting neoplastic transformation of pluripo- tent embryonal-like cells, lineage infidelity, or as a “wear-and-tear” phenomenon in pre- maturely senescent tumor cells.

In contrast to pigment storage due to the synthesis of melanin/neuromelanin by the neoplastic cells themselves, melanocytic colonization refers to an unusual form of symbiosis established between an other- wise conventional neoplasm and a scatter of melanocytes secondarily percolating from

the lesion’s melanocyte-containing micro- anatomical neighborhood. Most examples of this altogether rare pattern of cohabitation involve cutaneous-related sites [13, 14, 15].

As for primary CNS tumors, to the best of our knowledge, only three previous occur- rences of melanocytic colonization – each involving a meningioma as a substrate – have been reported [16, 17, 18].

Recently, we had the opportunity to study a hitherto unreported variant of the above scenario, one wherein melanocytes grafted themselves upon a choroid plexus papilloma. This was a consultation case from Cameroon, and the rather sparse clinical data indicated that the sample had been resected from a 13-year-old boy of African ethnicity.

Located within the right parietal lobe, the tumor was described as a homogeneously enhancing intraparenchymal mass communi- cating with the posterior horn of the lateral ventricle.

Light microscopy revealed a moderately cellular epithelial proliferation with tightly packed papillary to confluent, near-solid, architecture (Figure 1A). Irregularly lined up along nondescript vascular axes, individual tumor cells had copious cytoplasm with roundish contours, and harbored a sub- tly atypical nucleus. There was no detectable mitotic activity. The lesion’s most arresting feature was the presence of abundant brown intracytoplasmic pigment granules through- out the neoplastic cell population (Figure 1B). The pigment turned intensely black with Masson-Fontana’s silver impregnation (Fig- ure 1A – inset), and was partially sensitive to bleaching by hydrogen peroxide, whereas Prussian Blue staining gave a negative result.

The yield of immunohistochemistry was felt to have been hampered by suboptimal prean- alytical handling; nevertheless, appropriate expression of cytokeratin (clones AE1/AE3;

Dako, Glostrup, Denmark) was able to con- firm the epithelial nature of tumor cells (Fig- ure 1C). While the latter also exhibited faint to moderate reactivity with the melanosomal marker MELAN-A (clone A103; Dako), testing for this epitope surprisingly revealed a quite intensely stained secondary population of nonepithelial cells with dendritic to stellate morphology, not readily appreciated on routine slides (Figure 1D). Ubiquitously dispersed, these melanocytes tended to intri-

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cately intermingle with the tumor cells via their ramified processes (Figure 1E).

Based on the above findings, we posited a diagnosis of melanotic variant of choroid plexus papilloma (WHO grade I), along with a comment on the probable origin of the pigment from intratumorally recruited melanocytes.

Although unprecedented with regard to the nature of the host tumor, the plausibil- ity of our observation is nevertheless felt to be supported by the similarities it shares with previously reported examples of the

melanocytic colonization paradigm, both in the cutaneous realm and in the CNS. As for the latter, the present case also reinforces the perception that constitutional hyperpigmen- tation might possibly predispose to melanocytic colonization of tumors evolving within or contiguous to an anatomical compartment physiologically populated by melanocytes [16, 17, 18]. Conversely, profuse transfer of pigment granules from colonizing melanocytes to the cytoplasm of host tumor cells, as seen in our case, has not been a feature in any of the three previously reported me-

Figure 1. Histology and immunophenotype of choroid plexus papilloma colonized by melanocytes.

A: Overview of H & E-stained section to show architectural variability, alternating classical papillae supported by a vascular axe (asterisk), and irregular dehiscences within near solid areas. B: Close-up of two papillary fronds reveals stark contrast between erratic irregularity of the overall shape of tumor cells – many of them grotesquely ballooned by pigment storage – and the innocuous uniformity of nuclei. Pigmented globular densities corresponding to melanin precipitated on Biondi rings are appreciated (arrows). C: Im- munoreactivity of tumor cells for generic cytokeratin visualizes tight juxtaposition of plump cell bodies and, overlaid by the intrinsic color of melanin, produces a vaguely patterned mosaic of shades. D: In contrast, crisp staining for MELAN-A reveals a scatter of clearly individualized melanocytes (arrows). Note that a less intense labeling, one closely replicating the cytokeratin pattern, is also present in neoplastic epithelial cells. E: Colonizing melanocytes interacting with small clusters of papilloma cells via intricately branched dendritic processes. This pattern is reminiscent of the physiological symbiosis within the epithelial melanin unit. Microphotographs (A) and (B) represent H & E-stained slides. Inset in (A) represents Masson-Fontana impregnation. The immunohistochemical reactions depicted in (C) through (E) were developed with an al- kaline phosphatase detection kit (UltraView, Roche, Switzerland). Original magnification: (A, including inset)

× 100; (B) through (D) × 200; (E) × 400.

Clinical Neuropathology, DOI 10.5414/NP301200 – Letter to the editor

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ningiomas – although this is an elementary process within the normal epidermal melanin unit [19], and has been observed in the neoplastic epidermis as well [15].

Prior to the present observation, reported examples of pigmented choroid plexus neoplasms – also including one case of carcinoma [20] – indicate that choroid plexus epithelial cells are potentially able to elaborate neuromelanin [10,11] as well as melanosomes [9]. The former pathway has been speculated to result either from inappropriately long persistence or – on the contrary – accelerated senescence of tumor cells. Indeed, so-called

“Biondi rings” – a subcellular indicator of both physiological and pathological ageing [21] – have been known to occur in a sub- set of choroid plexus papillomas [22] and were seen in our case as well. On the other hand, a more generic – rather than mechanis- tic – argument of divergent differentiation/

lineage infidelity has been invoked to ac- count for the presence of true melanosomes.

Vague though it may be, this interpretation is nevertheless lent circumstantial evidential support per analogiam by the repeated oc- currence of aberrant melanosomes in some non-neural crest-derived CNS tumors in par- ticular gliomas as well [3, 5, 7]. For the sake of completeness, we further remark to have identified at least one case report on ependymoma – a close relative of choroid plexus tumors – containing both melanosomes and neuromelanin [4].

Tentative interpretations of melanocytic colonization tend to point out that several auto- or paracrine growth factors produced by tumors will also promote centripetal mi- gration of neighboring melanocytes [16, and references therein]. Moreover, since all reported cases to date involved a host tumor with epithelial or epithelial-like (i.e., meningothelial meningioma) character, an intrinsic propensity of melanocytes to engage in or- ganoid pairing apt to recapitulate the epidermal melanin unit might be invoked as well [19].

Exceptionally, the colonizing melanocytes themselves may be of neoplastic nature, as ex- emplified by some sporadic reports on squamous cell carcinoma or basal cell carcinoma amalgamated with melanoma in situ [14]. In our case, the absence of significant melanocytic atypia and detectable mitotic activity

rendered such an alternative utterly improb- able.

Notwithstanding the arguably limited dif- ferential diagnostic scope of our observation, we nevertheless feel prompted to articulate the following points. First, at variance from conventional neoplastic entities consubstan- tially defined by their melanotic character, the detection of melanin pigment in choroid plexus tumors does not, in itself, appear to determine the behavior of individual cases:

neither are melanized choroid plexus tumors intrinsically more aggressive [9, 10, 11, 12], nor does the presence of melanin exclude a diagnosis of choroid plexus carcinoma [20].

Second, the phenomenon of melanocytic colonization reported herein is apt to remind us of the physiological presence of some melanocytes in the choroid plexus stroma:

these, in turn, may occasionally be the source of primary intraventricular melanomas [23].

Acknowledgment

We wish to thank Professor Vincent de Paul Djientcheu (Service de Neurochirurgie, Hôpital Central de Yaoundé, Cameroun) for sharing this case.

Funding

There was no specific funding allocated to this study.

Conflict of interest

The authors declare that they are not aware of any conflict of interest.

References

[1] Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Ellison DW, Figarella-Branger D, Perry A, Reifen- berger G, von Deimling A. WHO Classification of Tumours of the Central Nervous System. Revised 4^th Edition. Lyon: IARC; 2016.

[2] Vajtai I, Yonekawa Y, Schäuble B, Paulus W. Mel- anotic astrocytoma. Acta Neuropathol. 1996; 91:

549-553. CrossRef PubMed

[3] Gupta RK, Saran RK, Sharma MC, Srivastava AK, Garg L. Melanosomal melanin pigment in pleomorphic xanthoastrocytoma, evidence for neuronal-glial origin: A case report with review of

(5)

the literature. Neuropathology. 2017; 37: 116-121.

CrossRef PubMed

[4] Chan AC, Ho LC, Yip WW, Cheung FC. Pigmented ependymoma with lipofuscin and neuromelanin production. Arch Pathol Lab Med. 2003; 127:

872-875. PubMed

[5] Antonelli M, Acerno S, Baldoli C, Terreni MR, Giangaspero F. A case of melanotic desmoplastic ganglioglioma. Neuropathology. 2009; 29: 597-601.

CrossRef PubMed

[6] Elizabeth J, Bhaskara RM, Radhakrishnan VV, Radhakrishnan K, Thomas SV. Melanotic differ- entiation in dysembryoplastic neuroepithelial tumor. Clin Neuropathol. 2000; 19: 38-40. PubMed [7] Jaiswal S, Agrawal V, Vij M, Sahu RN, Jaiswal AK, Behari S. Glioblastoma with melanotic differ- entiation. Clin Neuropathol. 2010; 29: 330-333.

CrossRef PubMed

[8] Stefanits H, Ebetsberger-Dachs G, Weis S, Haberler C. Medulloblastoma with multi-lineage differen- tiation including myogenic and melanotic ele- ments: a case report with molecular data. Clin Neuropathol. 2014; 33: 122-127. CrossRef PubMed

[9] Gong X, Liu C, Zhang L, Li Z, Bartley CM, Liu Z.

A primary pigmented choroid plexus papilloma located within the sella turcica: case report and literature review. World Neurosurg. 2017; 105:

1039.e13-1039.e18. CrossRef PubMed

[10] Reimund EL, Sitton JE, Harkin JC. Pigmented choroid plexus papilloma. Arch Pathol Lab Med.

1990; 114: 902-905. PubMed

[11] Vajtai I, Varga Z, Bodosi M, Vörös E. Melanotic papilloma of the choroid plexus: report of a case with implications for pathogenesis. Noshuyo By- ori. 1995; 12: 151-154. PubMed

[12] Watanabe K, Ando Y, Iwanaga H, Ochiai C, Nagai M, Okada K, Watanabe N. Choroid plexus papilloma containing melanin pigment. Clin Neu- ropathol. 1995; 14: 159-161. PubMed

[13] Bernaba BN, Binder SW, Cassarino DS. Myoepi- thelioma with melanocytic colonization (melanocytic myoepithelioma): a case report. J Cutan Pathol. 2009; 36: 697-701. CrossRef PubMed [14] Goeser M, DiMaio DJ. A colonization of basal

cell carcinoma by malignant melanoma in situ re- sembling a malignant basomelanocytic tumor.

Am J Dermatopathol. 2014; 36: e179-e182.

CrossRef PubMed

[15] Umlas J, Liteplo M, Ucci A. Squamous carcinoma in situ of the skin containing premelanosomes, with melanocytic colonization of the tumor. Hum Pathol. 1999; 30: 530-532. CrossRef PubMed [16] Dehghan Harati M, Yu A, Magaki SD, Perez-

Rosendahl M, Im K, Park YK, Bergsneider M, Yong WH. Clinicopathologic features and patho- genesis of melanocytic colonization in atypical meningioma. Neuropathology. 2018; 38: 54-61.

CrossRef PubMed

[17] Masui K, Suzuki SO, Kondo A, Iwaki T. A 6-year- old girl with an extra-axial mass in the middle cranial fossa. Brain Pathol. 2010; 20: 269-272.

CrossRef PubMed

[18] Nestor SL, Perry A, Kurtkaya O, Abell-Aleff P, Rosemblat AM, Burger PC, Scheithauer BW. Me- lanocytic colonization of a meningothelial meningioma: histopathological and ultrastructural findings with immunohistochemical and genetic

correlation: case report. Neurosurgery. 2003; 53:

211-214., discussion 214-215. CrossRef PubMed [19] Nordlund JJ. The melanocyte and the epidermal

melanin unit: an expanded concept. Dermatol Clin. 2007; 25: 271-281, vii. CrossRef PubMed [20] Dobin SM, Donner LR. Pigmented choroid plexus

carcinoma: a cytogenetic and ultrastructural study. Cancer Genet Cytogenet. 1997; 96: 37-41.

CrossRef PubMed

[21] Wen GY, Wisniewski HM, Kascsak RJ. Biondi ring tangles in the choroid plexus of Alzheimer’s dis- ease and normal aging brains: a quantitative study. Brain Res. 1999; 832: 40-46. CrossRef PubMed

[22] Navas JJ, Battifora H. Choroid plexus papilloma:

light and electron microscopic study of three cases. Acta Neuropathol. 1978; 44: 235-239. Cross- Ref PubMed

[23] Li CB, Song LR, Li D, Weng JC, Zhang LW, Zhang JT, Wu Z. Primary intracranial malignant melano- ma: proposed treatment protocol and overall sur- vival in a single-institution series of 15 cases combined with 100 cases from the literature. J Neurosurg. 2019; 1: 1-12. PubMed

Correspondence to Istvan Vajtai, MD

Service of Clinical Pathology, University Hospital Geneva, 1, Rue Michel-Servet, 1206, Geneva, Switzerland istvanvajtai@yahoo.com

Clinical Neuropathology, DOI 10.5414/NP301200 – Letter to the editor