Melanotic cerebral astrocytoma: case report and literature review

We describe the case of 47-year-old man with a cystic, melanotic temporal lobe astrocytoma who had a history of complex partial seizures. The tumor mass was made up of two histologically different regions: one consisted of spindle-shaped and pleomorphic cells often with foamy or vacuolated cytoplasm, while the other consisted of fairly uniform spindle-shaped cells, many of which contained dark-brown intracytoplasmic pigment. Desmoplasia was also noted in the latter region of the tumor. No features suggestive of malignancy, such as mitotic figures, necrotic foci or endothelial vascular proliferation, were observed throughout the tumor. Immunohistochemically, the tumor cells in both regions were positive for glial fibrillary acidic protein. Ultrastructural examination of the pigmented region showed the presence of melanosomal melanin in the tumor cells. Apart from the partial pigmentation, the entire histological picture resembled a pleomorphic xanthoastrocytoma. To our knowledge, only two cases of similar melanotic astrocytic tumors have been described previously. Interestingly, the astrocytic tumors in both of these patients were also clinically associated with epilepsy, were located in the temporal lobe, and were histologically benign. Received: 8 July 1996 / Revised, accepted: 10 September 1996     

Pigmented astrocytoma with suprasellar location: case report and literature review

A large suprasellar, partly cystic, contrast-enhancing tumor was resected from a 19-year-old woman who presented with bitemporal visual field defects and reduced visual acuity. Grossly, the tumor was brown and located in the subarachnoid space. Histologically, it was composed of spindle and pleomorphic cells, including giant tumor cells, with markedly pleomorphic nuclei. Reticulin fibers surrounded single cells and small groups of cells. Very few mitotic figures were found in the tumor, and no necrosis or microvascular proliferation was seen. The tumor thereby resembled a pleomorphic xanthoastrocytoma. Many of the tumor cells contained a dark-brown intracytoplasmic pigment, shown to be melanosomal melanin by ultrastructural examination. Immunohistochemical examination demonstrated that the pigment was present in glial tumor cells. Only four cases of pigmented astrocytic tumors have been published, none of these were suprasellar. Our patient received fractionated radiotherapy with a total dose of 48.6 Gy 14 months after gross total removal of the tumor. She is alive without relapse after 12-year follow-up.     

Melanosomal melanin pigment in pleomorphic xanthoastrocytoma,evidence for neuronal‐glial origin: A case report with review of the literature

We describe a unique case of pleomorphic xanthoastrocytoma (PXA) in a 19‐year‐old male presenting with the chief complaint of seizures. On radiology, the tumor was located in the temporal lobe. It was cortically based and solid cystic in nature. Light microscopy showed pleomorphic large polygonal cells with inclusions, nuclear clustering, lipidization, and foamy cytoplasm intermingled with spindle cells arranged in sweeping pattern and focally containing cytoplasmic brownish black pigment. The pigment stained black with Fontana?Masson stain and bleached with potassium permanganate. Gomori silver stain showed reticulin fibers surrounding individual tumor cells as well as groups of cells. On immunohistochemistry, tumor cells were positive for GFAP, S‐100 and focally for synaptophysin and CD34 but negative for HMB‐45. CD34 revealed a specific membranous pattern around individual cells as well as groups of cells along the fibers replicating a reticulin pattern. The ultrastructural examination showed supporting melanosomes, thus confirming the melanin pigment. Sequencing for BRAF V600E showed a heterozygous mutation. To our knowledge only five cases of PXA with melanin pigment have been reported and none of which described BRAF V600E mutation analysis. This case provides further insight into the origin and pathogenesis of pigmented astrocytic tumor, additionally highlighting the characteristic CD34 staining pattern.     

Pigmented ganglioneuroblastoma: relation of melanin and lipofuscin to schwannomas and other tumors of neural crest origin.

An unusual case of ganglioneuroblastoma containing melanin is presented. Electron microscopy revealed various stages of development of melanosomes in neoplastic cells of Schwann, the first direct demonstration in human material that these cells are malanogenic. The frequent occurrence of neuromelanin in autonomic ganglia and in ganglioneuromas is interpreted as the presence of altered lipofuscin. Review of ultrastructural and other observations indicates a relation between various pigmented tumors, the cell of Schwann, and other cells arising from the neural crest.     

Hemosiderin pigmentation of tumour cells in cerebellar pilocytic astrocytoma associated with post-traumatic hemorrhage in adults

The pilocytic astrocytoma is only rarely associated with gross intratumoral hemorrhage despite rich vasculature and blood vessel changes, accompanied often by perivascular depots of hemosiderin. We report an unusual case of pigmented cerebellar pilocytic astrocytoma presenting with posttraumatic hemorrhage in a 38-year-old man with no history related to the tumor. CT and MRI examination after head injury demonstrated unexpectedly the cystic lesion of 2 cm in diameter in the region of the right cerebellar hemisphere and vermis. The lesion was associated with hematoma and it was surgically removed 3 weeks after trauma. Histopathological examination revealed pilocytic astrocytoma tissue with broad hemorrhagic changes and with an unusual pattern of massive pigmentation of the cytoplasm of pilocytic astrocytes, consistent with hemosiderosis. Positive stains for iron and ferritin and ultrastructural study confirmed deposition of hemosiderin granules in the tumour cells. There was no evidence of melanin or melanosomes. This finding of hemosiderin accumulation in the cytoplasm of neoplastic astroglia seems to be analogous to post-hemorrhagic pigmentation of the normal Bergmann glia and subpial astrocytes. In the literature, the examples of neuroepithelial tumors with hemosiderin pigmentation of tumor cells have been rarely documented. To our knowledge, this is the first reported case of pigmented pilocytic astrocytoma exhibiting extensive intracellular hemosiderin deposition.     

Desmoplastic infantile astrocytoma: recurrence with malignant transformation into glioblastoma: a case report

Desmoplastic infantile astrocytoma (DIA) is an uncommon brain tumor of early infancy. The tumor is characterized by a lobar location, glial histology, and excellent prognosis after surgical removal. DIA and a similar tumor, desmoplastic infantile ganglioglioma (DIG) have been considered to be benign neoplasms, but the prognosis of DIA and DIG is currently under question as atypical and aggressive clinical features of the tumors have been reported. We encountered a patient who was diagnosed with DIA at the age of 22 months and exhibited tumor recurrence 8 years later. Surgical removal of the recurred tumor revealed that the tumor had transformed to overt glioblastoma. This case demonstrates that DIA is not an absolutely benign tumor and that careful clinical surveillance is needed during the follow-up period.     

A pigmented choroid plexus carcinoma: histochemical and ultrastructural studies.

A large tumor of the left lateral ventricle in a 3 1/2 year old male was diagnostic of malignant choroid plexus papilloma (choroid plexus carcinoma) as observed histologically. Focal neoplastic epithelial cells contained yellow-brown pigment which was not entirely compatible with melanin by histochemical techniques. Ultrastructurally, the tumor had definite evidence of choroid plexus origin. The neoplastic cells contained electron-dense and lamellar bodies, as well as structures of intermediate type. Premelanosomes were not observed. Thus there was no evidence for neural crest melanin. It is suggested that the pigment is probably lipofuscin and melanin derived from lipofuscin by "melanization" through pseudoperoxidation.     

S-antigen and rod-opsin immunoreactions in midline brain neoplasms of transgenic mice: similarities to pineal cell tumors and certain medulloblastomas in man

Transgenic mice expressing the large T-antigen of the simian virus 40 (SV 40) under the control of 1) the enhancer of Moloney murine sarcoma virus (MSV) and 2) the SV 40 promoter develop undifferentiated neuroectodermal tumors located in the midline of the dorsal brain surface, abnormalities in lens fiber differentiation and retinal dysplasia. In this study the brain neoplasms of six adult animals and the brain of one 11-day old mouse were examined by conventional histology and immunocytochemical demonstration of S-antigen, rod-opsin, neuron-specific enolase, neurofilaments (160 and 200 kDa) and glial fibrillary acidic protein. According to histologic criteria the neoplasms were characterized as "primitive" neuroectodermal tumors composed mainly of small cells with scanty and ill-defined cytoplasm. Neoplastic cells displaying immunoreactive S-antigen were found in five brain tumors; three of these tumors also contained a limited number of rod-opsin immunoreactive neoplastic cells. Some tumor cells had neurite-like processes containing immunoreactive neurofilament (200 kDa). No pathologic lesions were found in the brain of the 11-day old animal. Tumors in transgenic mice may resemble pineal cell tumors and a special subtype of medulloblastoma in man. These neoplasms contain S-antigen immunoreactive and also rod-opsin immunoreactive tumors cells in certain cases. The findings suggest that transgenic mice expressing the large T-antigen of SV 40 may become a valuable animal model for analysing the origin, histogenesis and development of primitive neuroectodermal tumors with photoreceptor-like features (pineal cell tumors and certain medulloblastomas).     

Melanin containing neurofibroma: case report with evidence of Schwann cell origin of melanin.

This case report describes a melanin-containing neurofibroma involving a spinal nerve root. Electron microscopy of the tumor shows that neoplastic Schwann cells are capable of melanogenesis. Although this capability is suggested in the literature, few reports provide ultrastructural confirmation. The likely identity between reported "cellular blue nevi of spinal nerve roots" and nerve sheath tumors is discussed. It is possible that pigmented nerve sheath tumors behave more aggressively than nonpigmented ones, although it is debatable.     

Melanotic cerebral ganglioglioma: evidence for melanogenesis in neoplastic astrocytes

Summary A composite melanotic glial-ganglionic tumor was resected from a 17-year-old girl who presented with a 5-year history of epilepsy. Grossly, the tumor was partly cystic, partly solid, located superficially in the temporal lobe. Histologically, its glial component was composed of spindle and pleomorphic cells, including tumor giant cells, which were associated with Rosenthal fibers, eosinophilic granular bodies and marked desmoplasia. The cells had immunohistochemical and ultrastructural features of astrocytes, and some were invested by incomplete basal lamina. Thus, the tumor had many features in common with pleomorphic xanthoastrocytoma. However, its most striking feature was the presence of melanin pigment in numerous neoplastic cells. Immunoelectron microscopy revealed glial fibrillary acidic protein-positive intermediate filaments in tumor cells bearing melanosomes and premelanosome, proving their astrocytic nature. This case demonstrates, for the first time, melanosomal melanogenesis in human cells with astrocytic phenotype, and provides additional evidence for the ability of central neuroepithelial cell derivatives to produce melanin.     

Pigmented pleomorphic xanthoastrocytoma: A rare variant and literature review

A 16‐year‐old male teenager presented with seizure and loss of consciousness for 20 min. Magnetic resonance imaging demonstrated a mass occupying the right medial temporal lobe. Histological examination revealed a non‐pigmented area with spindle‐shaped and large xanthomatous pleomorphic cells and a pigmented region with pigmented neoplastic cells with fascicular arrangement. Immunohistochemical studies showed the tumor was positive for GFAP and low index of Ki‐67. Considering the patient's history, clinical data and pathological findings, we rendered a rare variant named pigmented pleomorphic xanthoastrocytoma.     

Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems

Summary Four melanin pigment-containing intracranial tumors were found in three Long-Evans rats in the course of experimental oncogenesis by transplacental ethylnitrosourea (ENU). One of them was a leptomeningeal melanoma. Aside from the presence of scattered melanin-pigmented cells, the other three had the typical histological features of ENU-induced malignant nerve sheath tumors. Two of the three tumors were studied by electron microscopy and in tissue and organ culture systems. One of them demonstrated progressive melanogenesis in vitro; the other failed to produce more melanin and showed increasing differentiation, with a Schwannoma-like pattern by light microscopy. Melanosomes and premelanosomes were identified in both tumors by electron microscopy; the other fine structural features were those of malignant Schwannomas.These observations are relevant to the controversy on the histogenesis of pigmented nerve sheath tumors occasionally encountered in man and on the relationship of these tumors to pigmented nevi. The findings in the present study support the view of Masson that neoplastic nerve sheath cells are capable of melanogenesis.Supported by Research Grant CA 11689 from the National Cancer Institute, Graduate Neuropathology Training Grant 5 T01 NS 5500-09 and by Special Fellowships 1F03 NS 55632 (A.M.S.) and 1F11 NS 2629 (F.K.C.) from the National Institute of Neurological Diseases and Stroke, U.S.P.H.S.     

Ependymoma with “granular cell” features: Report of two cases

We report two cases of ependymoma which showed prominent “granular cell” changes of the cytoplasm. The patients were a 7‐year‐old boy with a tumor in the cerebellum (case 1) and a 70‐year‐old man with a tumor in the frontal lobe (case 2). The tumor of case 1 showed a histopathological appearance of ependymoma containing many focal aggregates of large polygonal cells in which the cytoplasm was stuffed with numerous eosinophilic granules. The tumor of case 2 predominantly showed the features of papillary ependymoma, and some tumor cells were swollen and contained similar eosinophilic granules. Intracytoplasmic granules in both tumors were immunoreactive for GFAP and ubiquitin, but not for epithelial membrane antigen, CD68 or mitochondria. Ultrastructurally, they were found as aggregates of membrane‐bound, electron‐dense, globular structures. Karyotypic analysis of the tumor in case 1 demonstrated 2, 11 and 12 trisomies. Intracytoplasmic eosinophilic granules occasionally occur in astrocytic and oligodendroglial neoplasms, but an appearance of similar granules is very rare in ependymoma. The two cases presented here may represent a new histopathological variant of ependymoma, and the term “granular cell ependymoma” is appropriate for them.     

Melanin in the rat brain

Melanin was measured in various parts of the rat brain by a spectrophotofluorometric assay. This method could detect natural, Sepia melanin as well as melanin synthesized from L-DOPA. Contrary to published expectations of other investigators, measurable amounts of melanin were found in the brain of albino as well as pigmented rats. The highest concentrations of melanin occurred in the pons-medulla and midbrain, but all regions within the blood-brain barrier contained greater concentrations than samples from many other tissues in the body. No significant change in the melanin content was found after various endocrine manipulations such as removal of the pituitary, pineal, adrenals, thyroid, testes, or ovaries, exposure to constant illumination or darkness, and daily injection for 5 weeks of alpha-MSH, Pro-Leu-Gly-NH2 (MIF-I) or melatonin. As expected, retinal tissue from black-hooded rats contained extremely high levels of melanin whereas that from albino rats contained no melanin. It is thought that the presence of melanin in the brain of albino and pigmented rats may have a function which is still unknown.     

Melanotic craniopharyngioma: a report of two cases

We report a 74-year-old woman and a 50-year-old woman with similar histories of headache and visual disturbance who were found to have adamantinomatous craniopharyngiomas which contained melanin pigment. This finding was confirmed by the Masson Fontana method and ultrastructural studies. These are only the second and third cases reported describing melanin pigment within a craniopharyngioma. The finding of melanin in craniopharyngiomas attests to their similarities with odontogenic tumors of the jaw, which can also contain melanin pigment and also supports the hypothesis that the histogenesis of these neoplasms derives from the vestiges of Rathke’s pouch epithelium. Received: 1 September 1998 / Revised: 22 February 1999 / Accepted: 15 March 1999     

Desmoplastic infantile ganglioglioma with calcification

Desmoplastic infantile gangliogliomas (DIGs) are rare intracranial, cystic tumors, usually detected within the first 2 years of life. Histologically, these tumors are characterized by intense desmoplasia and a divergent astrocytic and neuronal differentiation. Less than 60 well‐documented cases of this extremely rare tumor are reported in the literature. We present the case of a 10‐month‐old male child presenting with a large, cystic, intracranial lesion and having the characteristic histological features of a DIG. In addition, the lesion also showed focal areas of calcification within the tumor, not usually considered a feature of this entity. The present case extends the reported spectrum of this rare entity and describes the unusual occurrence of calcification within the lesion.     

Pigmented central neurocytoma

Central neurocytoma is a low-grade neuronal neoplasm that occurs most often within the lateral ventricles. We report the case of a 60-year-old woman who presented with gait problems, headache and memory loss. Preoperative evaluation demonstrated a heterogeneous, hypervascular and partially cystic mass in the left lateral ventricle. Histopathological examination revealed characteristic features of central neurocytoma, including immunoreactivity for synaptophysin, as well as the unusual feature of abundant pigment in the cytoplasm of tumor cells. Special stains revealed iron, consistent with hemosiderin, but found no evidence of melanin or melanosomes. Previous reports of pigmented central neurocytoma have described the presence of lipofuscin or neuromelanin. To our knowledge, the present case represents the first example of pigmented central neurocytoma secondary to hemosiderin deposition.     

Papillary glioneuronal tumor--a new tumor entity

Glioneuronal neoplasms of the CNS comprises a heterogeneous group of generally low-grade tumors expressing glial and neuronal cells of varying differentiation. Recently, a new variant of the glioneuronal tumors has been identified. We present a case of a glioneuronal tumor located in the left frontal lobe of a 16-year-old boy who developed seizures 6 months after brain concussion. MR scan demonstrated an irregular, but well circumscribed, mixed cystic and solid tumor with contrast enhancement in the solid part. Histology showed a papillary glioneuronal tumor. The tumor is indolent with no sign of recurrence after gross total resection.