Meningeal melanocytoma of the brain and oculodermal melanocytosis (nevus of ota): case report and literature review

Meningeal melanocytoma of the brain and oculodermal melanocytosis (nevus of ota): case report and literature review

Neoplasm Meningeal Melanocytoma of the Brain and Oculodermal Melanocytosis (Nevus of Ota): Case Report and Literature Review Vafa Rahimi-Movaghar, M...

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Meningeal Melanocytoma of the Brain and Oculodermal Melanocytosis (Nevus of Ota): Case Report and Literature Review Vafa Rahimi-Movaghar, M.D.,* and Mehrbod Karimi, M.D.† *Department of Neurosurgery, †Department of Pathology, Khatam-ol-anbia Hospital, Zahedan University of Medical Sciences, Zahedan, Iran

Rahimi-Movaghar V, Karimi M. Meningeal melanocytoma of the brain and oculodermal melanocytosis (nevus of ota): case report and literature review. Surg Neurol 2003;59:200 –10. BACKGROUND

Meningeal melanocytomas are rare benign pigmented tumors of meningeal melanocytes. Nevus of Ota is a melanocytic pigmentation of the sclera and the skin adjacent to the eye. We report a rare case of parietal convexity meningeal melanocytoma associated with ipsilateral mucocutaneous melanosis and review the literature. METHODS

A 17-year-old man presented with headache and blindness. There was left scalp and facial mucocutaneous melanosis. During surgery, speckled hyperpigmentation was seen in all layers of the scalp, bone, dura, and even ependyma. Pathologic examination of the tumor and scalp consisted of light microscopy and immunohistochemistry. In a literature review, the demographics (age, sex), clinical characteristics (site of lesion, duration of symptoms), therapeutic options (surgical excision, radiotherapy), and prognosis (recurrence, death, death related to the disease, and follow-up) were analyzed. For statistical analysis we used the independent sample t-test and ␹2 tests. RESULTS

Ninety-five cases (45 intracranial and 50 spinal) of meningeal melanocytoma have been reported. The median age of patients with intracranial lesions (40 years) was significantly lower than that of patients with spinal lesions (49 years) (p ⫽ 0.016). Of the 95 patients, 57.9% were female. In the nervous system, melanocytes are more common in the infratentorial and cervical areas, but more than half of the tumors have been located in the supratentorial region and the thoracic spine. In 46 months median follow-up, tumor recurrence rate and tumor related death rate were 26.3% and 10.5%, respectively. These were not statistically significant for different therapeutic modalities. There was a trend toward shorter survival for patients who underwent subtotal tumor re-

Address reprint requests to: Dr Vafa Rahimi-Movaghar, Department of Neurosurgery, Khatam-ol-anbia Hospital, Zahedan, Iran. Received June 6, 2002; accepted October 3, 2002. 0090-3019/03/$–see front matter doi:10.1016/S0090-3019(02)01052-2

section without radiotherapy compared with other groups. CONCLUSION

The prognostic criteria, differential diagnosis, and the embryological aspects of meningeal melanocytoma are discussed with a review of the related literature. © 2003 Elsevier Science Inc. KEY WORDS

Immunohistochemistry, melanocytes, meningeal melanocytoma, meningeal tumors, melanotic meningioma, nevus of Ota.

eningeal melanocytomas are rare, benign, pigmented tumors of meningeal melanocytes occurring most frequently in the posterior fossa and along the spinal cord, producing neurologic deficits by mass effect rather than by infiltration of adjacent nerve structures [65]. Radiologic features are also similar to those of meningiomas. However, immunohistochemistry and electron microscopy can differentiate this tumor from meningiomas. Nevus of Ota (oculodermal melanocytosis [5] or naevus fuscocaeruleus ophthalmomaxillaris) is an extensive, blue, patch-like area of dermal melanocytic pigmentation of the sclera and the skin adjacent to the eye because of the presence of dermal melanocytes [63]. It was first described by Hulke in 1861 and Ota later described 26 cases in the Japanese population in 1939 [47]. To study the demographics, clinical features, and impact of therapeutic options (complete tumor resection with and without radiotherapy; incomplete resection followed by radiotherapy; and incomplete resection alone) on outcome, we reviewed all 95 cases reported (including present case). Furthermore, we include a rare case of a parietal convexity meningeal melanocytoma associated with a nevus

M

© 2003 by Elsevier Science Inc. 360 Park Avenue South, New York, NY 10010 –1710

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of Ota. It is noted in the literature that meningeal melanocytoma and nevus of Ota can occur concurrently [3,6,50].

Clinical Materials and Methods REVIEW OF THE LITERATURE SELECTION OF CASES. We have included only those cases described in sufficient detail to allow us to form independent conclusions. We agree with Winston et al [73] in excluding the following cases: the melanoblastic meningioma of Bailey and Bucy, which was probably a malignant melanoma as evidenced by the large number of pigmented lesions over the surface of the cerebral hemispheres and within the cerebellum, and by the presence of many mitotic figures. Several series include the cases mentioned by Russell and Rubinstein but these had insufficient detail of the anatomic features for the reader to form an independent opinion about the diagnosis. The second case of Ray and Foot contained nuclear palisading and was clearly invading bone and therefore was excluded. Three of the cases reported by Graham et al were rejected: Cases 1 and 3 because of extradural lesions and Case 2 because it was stated to be a malignant melanoma [73]. We agree with Ibanez et al [27] in excluding the case of the “multiple intra and extrameningeal tumors” of Scott et al [59]. A case report by Shinoda with optic nerve head melanocytoma was also rejected, because it had no pathologic diagnosis [61]. CLINICAL STUDY We reviewed and evaluated the demographics (age, sex), clinical characteristics (site of lesion, duration of symptoms), therapeutic methods (surgical excision, radiotherapy), and outcome (recurrence, death, death related to the disease, and follow-up) for all cases in the literature except for the above exclusions. For statistical analysis we used the independent sample t-test and ␹2 tests; significance was defined as p ⬍ 0.05.

Case Report HISTORY A 17-year-old male Caucasian presented with headache and blindness in both eyes of 4 months’ duration. Visual loss was gradual and progressive, but of unknown duration. He had been incarcerated for 38

Computed tomography scan after IV contrast revealing a nonhomogeneously enhancing lesion located in the left parietal region, with shift of ventricles and midline structures to the right.

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months. The patient’s medical history was significant only for left scalp and facial hyperpigmentation at least since early childhood. EXAMINATION The patient’s general medical examination was normal except for left scalp and facial cutaneous melanosis including left conjunctiva and sclera melanosis. He had progressive lethargy, periods of disorientation and confusion, and higher cortical function impairment. Visual acuity testing revealed no light perception in either eye and funduscopic exam showed bilateral secondary optic atrophy. There were no motor deficits in four limbs or cranial nerves deficits. RADIOLOGIC EVALUATION The patient had a computed tomography (CT) scan of the brain without and with IV contrast. On the non-contrasted CT scan, the lesion was very slightly hyperdense with a vague margin and surrounding edema. Intravenous contrast revealed a nonhomogeneously enhancing lesion located in the left parietal region, with shift of ventricles and midline structures to the right (Figure 1). Based on the CT scan, the patient was thought to have a left parietal meningioma.

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Microscopic photograph showing a cellular neoplasm containing pigmented tumor cells with coarse brownish cytoplasmic granules without pleomorphism (hematoxylin and eosin, original magnification ⫻300).

OPERATION All layers of subcutaneous (SC tissue, fascia, muscle, periosteum, bone, and dura had black pigmentation. Upon opening the dura, a black, encapsulated mass was encountered. The lesion was distinct from the brain but was firmly attached to the dura. The mass was vascular, but bleeding was controlled without difficulty. It was soft and suctionable, and complete resection was achieved. PATHOLOGIC FINDINGS Light microscopic examination showed sheets of tumor tissue with focal areas of whorled pattern and scattered intra- and extracytoplasmic brownish pigments, but no pleomorphism, necrosis, or abnormal mitosis was seen. The individual tumor cells had vesicular nuclei with inconspicuous nucleoli and indistinct eosinophilic cytoplasm (Figure 2). Iron staining was negative. Immunohistochemistry (IHC) revealed positive reactions to HMB-45 (Figure 3) and S-100 in neoplastic cells with nonspecific background and focally positive epithelial membrane antigen (EMA) in some neoplastic cells. The histopathology and IHC findings were consistent with meningeal melanocytoma. Biopsies from the dura and ependyma were also taken during the operation; scattered melanocytes were seen in these samples. Skin biopsy revealed elongated dendritic melanocytes scattered

among the collagen bundles, located mostly in the upper third of the dermis. POSTOPERATIVE COURSE The patient’s postoperative course was uneventful, with no new neurologic deficits. Headache and confusion resolved completely. His vision in both eyes was unchanged 10 months postsurgery.

Results To our knowledge, including the present case, 95 cases (45 intracranial and 50 spinal) of meningeal melanocytoma, have been reported to date (Table 1). The median age was 45 years (ranging 5 months–74 years). The median age of patients with intracranial lesions was 40 and for those with intraspinal lesions it was 49. It was significantly lower in patients with intracranial lesions (p ⫽ 0.016). Fifty-five of 95 patients (57.9%) were female. The median duration of symptoms before diagnosis was 29 months (0 –168 months). Meningeal melanocytomas are located in the posterior fossa [10,46,58], medulla oblongata [64], anterior to the medulla and pons [39,68], cerebellopontine angle [23,43,52], tentorium [28], Meckel’s cave [8,32,35,73], cavernous sinus [19], pineal region [13], planum sphenoidale [41],

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Immunohistochemical microscopic photograph showing positivity for HMB-45 in the neoplastic cells with nonspecific background reaction (original magnification ⫻300).

sphenoid wing [41], frontal lobe [3,29], rolandic area [2,50], parietal lobe [7], temporal lobe [45], suprasellar region[66], foramen magnum [14,36], cervical and thoracolumbar regions [1,4,11,12,15, 20,21,24,25,27,30,33,38,42,45,49,60,62,73], and the cervical root [7,57,65]. A case of extensive supra- and infratentorial and cervicothoracic tumor [48], a case of craniocervical tumor [70], one case of multiple lesions in the cervical and the thoracic spine [11], and one in thoracic and lumbar areas [24] have also been reported. The site of tumor was

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intracranial in 45 cases (47.5%) and along the spine and spinal roots in 50 cases (52.5%). Tumors were located supratentorially in 25 cases (26.3%) and infratentorially in 18 cases (19%). In the spine, tumors were cervical in 19 cases (20%), thoracic in 25 cases (26.3%), lumbar in 4 cases (4.2%), and at more than one site in 4 cases (4.2%). Follow-up ranged up to 35 years, with a mean of 46 months. Fifty-two patients (54.7%) underwent complete tumor resection; 8 of these patients underwent additional postoperative radiotherapy. In 33 patients (34.7%) a sub-

Summary of Cases of Meningeal Melanocytoma

Median age Sex Median duration of symptoms Location

Mean follow-up Death Tumor-related death

(intracranial lesions) (intraspinal lesions) Male Female intracranial spine and spinal roots supratentorial infratentorial cervical thoracic lumbar more than one site

45 years (5 months–74 years) 40 years 49 years (p ⫽ 0.016) 40 cases (42.1%) 55 cases (57.9%) 29 months (0–168 months) 45 cases (47.5%) 50 cases (52.5%) 25 cases (26.3%) 18 cases (19%) 19 cases (20%) 25 cases (26.3%) 4 cases (4.2%) 4 cases (4.2%) 46 months (0 week to 35 years) 19 cases 10 cases (10.5%)

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Recurrence Rate and Death Rate for Different Therapeutic Modalities

THERAPEUTIC MODALITY

GROUP 1

GROUP 2

GROUP 3

GROUP 4

P

No. of patients (%) Death related to the disease (%) Recurrence rates (%)

8.4 12.5 37.5

46.3 5 21.4

15.8 6.7 42.9

18.9 23.5 35.3

⬎0.05 ⬎0.05

Group 1. Complete tumor resection with radiotherapy. Group 2. Complete tumor resection without radiotherapy. Group 3. Subtotal tumor resection with radiotherapy. Group 4. Subtotal tumor resection without radiotherapy. 10 cases of partial tumor resection, biopsy, and unknown cases were omitted.

total resection was performed; 15 of these patients underwent additional postoperative radiotherapy. In 10 others, surgical removal was partial, biopsy, or not recorded. Twenty-five patients (26.3%) underwent radiotherapy. The median radiation dose was 30 Gy (range 9 –105 Gy). There was one case of stereotactic radiosurgery in which 25 Gy of radiation was delivered to the tumor margin [32]. Recurrent disease occurred in 25 cases (26.3%); 60 patients (63.2%) were reported to be well without recurrent tumor. Ten others were not recorded. Nineteen of the 95 patients were dead at the time of reporting, 10 from their tumors (10.5%), 4 from unrelated causes and 5 from unknown causes. The survival rates, recurrence rates, and recurrence at 1, 2, 3, 4, and 5 years after surgery were calculated for four therapeutic modalities: 1) complete tumor resection with radiotherapy, 2) complete tumor resection without radiotherapy, 3) subtotal tumor resection with radiotherapy, and 4) subtotal tumor resection without radiotherapy (Table 2). Death related to the disease occurred in 12.5%, 5%, 6.7%, and 23.5% of cases, respectively. Recurrence rates including malignant transformation and metastasis were 37.5%, 21.4%, 42.9%, and 35.3%, respectively. The observed differences in above results and in the rates of recurrence between 1 and 5 years after surgery were not statistically significant (p ⬎ 0.05). There was a trend toward shorter survival for patients who underwent subtotal tumor resection without radiotherapy compared with other groups. The rates of recurrence at 1, 3, 4, and 5 years after surgery were 3.2%, 8.4%, 9.5%, 16.8%, and 21.1%, respectively (Figure 4). The rate increases despite surgery and radiotherapy.

studies of Limas and Tio demonstrated that the cell of origin of the so-called pigmented meningiomas is the melanocyte and not the meningothelial cell [38]; they proposed the term “meningeal melanocytoma” to describe these tumors. Melanocytes are widely distributed throughout the leptomeninges and they occur in the highest concentration ventrolateral to the medulla oblongata [10]. The highest concentration of melanocytes in the spinal leptomeninges occurs at the upper cervical levels [53,55,65]. In the nervous system, melanocytes are more common in the infratentorial and cervical areas, but more than half of the tumors have been reported in the supratentorial region and the thoracic spine. In other words, the distribution of meningeal melanocytoma is the same as the other adult tumors, including meningioma. A common feature of both intracranial and intraspinal meningeal melanocytomas is their propensity to arise in proximity to cranial and spinal

Discussion ANATOMIC LOCATION Pigmented cells are normally found in the leptomeninges, and according to Virchow, were first described by Valenti [10]. The electron microscopic

Recurrence rate of meningeal melanocytoma. It increases despite surgery with or without radiotherapy.

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nerves as they exit the brainstem and spinal cord, respectively. Excessive pigmentation of the leptomeninges, socalled meningeal melanocytosis because of an increase in the number of melanocytes and the amount of melanin produced, is occasionally encountered and may be associated with pigmented cutaneous nevi [54]. There have been a few case reports of benign or malignant tumor of meningeal melanocytes in this setting [54,56]. CLASSIFICATION Brat et al divided primary melanocytic neoplasms into three categories: 1) low-grade melanocytomas with benign histologic features and excellent prognosis, 2) high-grade melanomas with cellular anaplasia and necrosis, but unexpectedly favorable outcome (compared to metastatic melanoma), and 3) intermediate neoplasms that cannot be classified as melanocytoma or melanoma [7]. The obvious distinctive features were listed as follows: the cytoarchitecture of the neoplasm, mitotic index (melanocytomas had 0 to 1 per 10 high-power fields), labeling index (higher in melanomas than in melanocytomas), the nuclear morphology and pleomorphism, the existence of coagulative necrosis, and evidence of microscopic CNS invasion. The differential criteria for metastatic (secondary) melanomas are primarily based on the presence of frequent necrosis and cellular anaplasia besides invasion of the CNS. EPIDEMIOLOGY The nevus of Ota is not uncommon in Asian people, but is comparatively rare in other races. In Japan, 0.4 to 1.0% of all patients seen in dermatologic clinics are affected. Although typically sporadic, it may occur in successive generations. Eighty percent of patients are women. The age at onset shows two peaks: one in infancy, the other in adolescence, but the nevus may fluctuate in extent and color [3]. CLINICAL PRESENTATION A variety of neurologic and clinical features may be seen with meningeal melanocytoma, including signs and symptoms of an expanding mass, hydrocephalus [14], seizures, chronic basal meningitis, single or multiple cranial nerve palsies, chronic spinal arachnoiditis, psychiatric disturbances, stillbirth, intracranial hemorrhage of the meninges, subarachnoid [42], or subdural space, myelopathy, and radiculopathy [16,18]. Nevus of Ota is often present at birth (60%) or appears at puberty (40%). It becomes progressively darker in childhood and persists in adult life [40]. The pigmentation is often speckled and is com-

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posed of deeper bluish and more superficial brownish elements, which do not always coincide. The two colors are perhaps best seen on the eye, where the affected sclera is blue and the conjunctiva brown. The distribution is usually restricted to the first and second divisions of the trigeminal nerve and commonly affects the forehead, temple, or eyelids. There may be melanosis of the palate, pharynx, nasal mucosa, or tympanum. An ocular effect is not always observed, as was noted by Fitzpatrick et al. The distribution is usually, but not always, unilateral [17]. NEUROLOGIC INVOLVEMENT IN NEVUS OF OTA In three cases of nevus of Ota, ballooning of the posterior fossa to produce a step-like deformity of the occiput has been reported. There has also been one case of facial hemiatrophy. Three out of 15 patients with nevus of Ota had light pigmentation in the optic disc in the affected eye [31]. The pupillary light reflex may be slower in the affected eye [3]. In rare instances, malignant melanoma has developed in the skin or eye, including choroid, iris, or the orbit. In 12 patients, the nevus of Ota was associated with intracranial melanoma [3,67]. Intracranial melanomas associated with Ota’s nevus have been found in the cerebral hemisphere, the optic chiasm, the optic tract, and the pineal gland [56]. Blue nevus of the scalp has been reported in association with meningeal melanocytoma [2]. There is a report of a patient with congenital nevus of Ota who had a localized tumor that resembled melanocytoma [3]. There were two other cases of meningeal melanocytoma associated with ipsilateral Ota’s nevus [6,50]. Nevi of Ota have been found to be associated with spinocerebellar degeneration, vascular disease of inflammatory origin (Takayasu’s arteritis) or defect (Klippel-Trenaunay syndrome), cerebral arteriovenous malformaton, tuberous angiomas, phacomatosis (Recklinghausen’s disease), or pigmentovasclar phacomatosis [50]. As with other cutaneous and extracutaneous nevi, transformation to malignant nevus or melanoma or the development of biologic aggressiveness is rare. PATHOPHYSIOLOGY DEVELOPMENT OF MELANOCYTES AND LEPTOMENINGEAL MELANOSIS. Melanoblasts are de-

rived from the neural crest. They can be found as early as the 10th fetal week and they differentiate into fusiform elements, namely melanocytes [3]. Some cells rise to the dermoepidermal junction to produce melanin. Other melanocytes are arrested

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in migration and remain in the dermis, where they may form the cellular blue nevus, a mongolian spot, a nevus of Ito, or a nevus of Ota. The arrested migration of melanoblasts from the neural crest leads to the appearance of other pigmentary abnormalities in the nerve fibers, meninges, ocular structures, and inner ear. The meninges themselves are formed from contributions of the mesenchyma of the prechordal plate, the mesoderm, and the neural crest. The neural crest contributes to the pia mater, including melanotic cells. According to this theory, it is reasonable to assume that melanocytoma of the meninges represents an area of meningeal melanocytosis that has undergone a nodular neoplastic proliferation [6]. Macroscopic pigmentation of the meninges can commonly be seen over the ventral medulla and pons, cerebral peduncle, and sylvian fissure [18,34,72]. There is a case report of identical lesions in both adrenal glands and the left renal capsule, the structures containing neural-crest-derived cells outside the CNS [46]. This indicates that neurocutaneous melanosis is actually a phacomatosis caused by congenital dysplasia of the neuroectodermal melanocyte precursors, resulting in excessive (focal or diffuse) proliferation of melaninproducing cells in the skin and pia mater [56]. This pattern of leptomeningeal involvement is unlike metastatic melanoma, which typically produces focal pigmented lesions of the leptomeninges. Melanotic pigmentation of the skull, periosteum, meninges beneath the nevus and ventricular ependyma, choroid plexus, and cerebral parenchyma, as in our case, has rarely been found at operation [16]. Melanocytic lesions of the conjunctiva or sclera are derived from one of three types of melanocytes: dendritic, nevus, or fusiform. The fusiform mesenchymal melanocytes are deeper in the subepithelial tissue and are frequently in aggregations. They are clinically evident as the mongolian spot (in the skin) and as the ocular conditions of congenital oculodermal melanosis, melanosis oculi, blue nevus, and pigmented episcleral spots [37]. IMAGING CT, MRI, and angiography of meningeal melanocytoma and meningioma are similar. The imaging appearance of meningeal melanocytoma is variable depending on the degree of melanization. The CT appearance is characterized by iso- to hyperattenuating lesions with variable contrast enhancement [48]. The MR appearance is strongly influenced by the paramagnetic effects of melanin, which causes shortening of T1 and T2 relaxation times [16]. Therefore, the MR appearance of these lesions is

Rahimi-Movaghar and Karimi

generally high signal intensity on T1-weighted images and diminished signal on T2-weighted images, with enhancement after contrast administration [22]. DIFFERENTIAL DIAGNOSIS The differential diagnosis of primary pigmented lesions of the leptomeninges includes pigmented meningioma, metastatic malignant melanoma, primary malignant melanoma, meningeal melanocytoma, melanotic schwannoma, and melanoblastosis [48]. Meningeal melanocytoma and primary malignant melanoma of the leptomeninges are similar in their origin from leptomeningeal melanocytes, but actually represent both ends of the spectrum, ranging from a lesion that is benign in appearance and behavior to one that is malignant. DIFFERENTIAL DIAGNOSIS OF PIGMENTED MUCOCUTANEOUS LESIONS Pigmented lesions of the eye are probably best distinguished by classifying melanocytic lesions into conjuctival melanosis, nevi, acquired melanosis, and conjunctival melanoma. The congenital melanosis is two types; epithelial and subepithelial. Oculodermal melanosis (The nevus of Ota) is an ipsilateral pigmentation of the periocular skin (including the eyelids) and melanosis oculi (including conjunctiva, episclera, and sclera). In contrast to benign epithelial melanosis, in which the pigment is in the conjunctival epithelium, the pigment is deep to the conjunctiva (in the episclera) and does not move with the conjunctiva. It is most commonly seen in blacks and orientals. Patients with melanosis oculi or nevus of Ota have a low risk of developing a uveal melanoma or a primary orbital melanoma, and the tendency to develop choroidal melanoma is restricted to Caucasians; conjunctival melanoma has not been reported. Conjunctival nevi do not extend onto the cornea. Nevi are freely movable on the conjunctiva except at the limbus; attachment to the episclera or sclera is suggestive of melanoma. Malignant change is rare. Benign nevi tend to increase in growth, vascularity, or pigment during puberty. Secondary acquired melanosis is a physiologic or irritant-induced increase in pigmentation of the conjunctiva caused by irradiation, hormonal changes (such as those from Addison’s disease or pregnancy), chemical irritation (related to arsenic or chlorpromazine hydrochloride), or chronic inflammatory conjunctival disorders (vernal keratoconjunctivitis, xeroderma pigmentosum, and tra-

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Differential Diagnosis of Localized Pigment Tumors of Meninges

Immunohistochemistry Vimentin S-100 protein HMB-45 Keratin EMA Leu 7 Ultrastructure Basal membrane Desmosomes Premelanosomes Long-spacing collagen Prominent nucleoli

MENINGIOMA

SCHWANNOMA

MELANOCYTOMA

MELANOMA

⫹ ⫺ ⫺ ⫹focally ⫹ ⫺

⫹ ⫹ ⫺ ⫺ ⫺ ⫹

⫹ ⫹ ⫹ ⫺ ⫺ ⫺

⫺ ⫹ ⫹⫹ ⫺ ⫺ ⫺

⫺ ⫹ ⫺ ⫺ ⫺

⫹ ⫺ ⫺ ⫹ ⫹

⫺ ⫺ ⫹ ⫺ ⫹

PRESENT

CASE

NA ⫹ ⫹ NA ⫺ NA

⫹Majority present; ⫺ majority absent.

choma). Depending on the source, it is frequently bilateral. Primary conjunctival melanomas are rare, but secondary types are associated with extraocular extension of uveal or ciliary body melanoma. Rarely, a metastatic conjunctival lesion can develop from a skin melanoma [37]. GROSS APPEARANCE The gross appearance of meningeal melanocytoma as seen during surgery or at autopsy is that of a well-encapsulated, nodular, dark brown or coal black, heavily pigmented tumor that may be attached to the dura but is well demarcated from the surrounding tissue. A meningioma may mimic this gross appearance if large amounts of hemosiderin are present within the lesion from previous episodes of hemorrhage [48]. PATHOLOGY The component cells may range in shape from spindle or fusiform to polygonal and epitheloid with abundant pale or eosinophilic cellular cytoplasm. The nuclei are usually large, often oval or elongated. Prominent nucleoli are described [45,62,69]. The cells are arranged in whorls, sheets, bundles, or nests, surrounded by a fine network of reticulin fibers. Necrosis and hemorrhages are generally absent, though O’Brien et al reported minimal necrosis, and the mitotic figures are described as few, scanty, occasional, or single [45,65,73]. Abbott and Keegan reported psammoma bodies and calcification. Histologic examination of cells obtained from pigmented tumors is of limited value other than to demonstrate intracytoplasmic melanin. The tumor cells may be variously arranged and show differing degrees of melanization. The pigment stains negatively for iron. Only a few authors have reported

scant iron-positive pigment [6,33,45]. The cells have a uniform cytologic appearance, without areas of anaplasia. The absence of cytological signs of malignancy or significant mitotic activity, necrosis, inflammatory infiltrates, or invasion of adjacent tissue all contradicts the diagnosis of melanoma. Ultrastructurally, meningeal melanocytomas contain a large number of melanosomes and premelanosomes at different stages of differentiation. Additionally, meningeal melanocytoma cells lack desmosomes and interdigitating cytoplasmic processes characteristic of meningiomas. IMMUNOHISTOCHEMICAL FEATURES OF PIGMENTED TUMORS OF THE MENINGES Immunohistochemical analysis is indispensable in differentiating meningeal melanocytoma from other similar pigmented lesions (Table 3). Meningeal melanocytoma is characterized by a positive immunoperoxidase staining for antimelanoma antibody (HMB-45), S-100 protein, and vimentin antibodies, and by a negative reaction to EMA. Vimentin is the predominate intermediate filament of the cytoskeleton in cells of mesenchymal origin. It is important here because it usually appears in meningeal melanocytoma but is only rarely present in malignant melanoma. Melanocytic meningioma is characterized by a positive reaction to EMA and vimentin, and by a negative reaction to HMB-45 and S-100 protein. A positive reaction to HMB-45 and S-100 protein, in the absence of a reaction to EMA, provides a reliable diagnostic criterion for the diagnosis of a pigmented lesion, excluding meningioma. The histologic differentiation between malignant melanoma and melanocytoma can be even more difficult. The overall lack of mitotic activity, the lack

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of nuclear pleomorphism and hyperchromaticity, and the indolent growth of the mass all point to melanocytoma versus melanoma. The presence of prominent nucleoli is a regular feature of meningeal melanocytoma. Anti-Leu-7 has been localized in tumors of Schwann cells and oligodendroglia that contain myelin-associated glycoprotein [33]. The absence of reactivity to Leu-7 excludes a diagnosis of melanocytic schwannoma.

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5. 6. 7. 8.

TREATMENT In 46 months’ median follow-up for 95 cases, tumor recurrence rate and tumor-related death rate were 26.3% and 10.5%, respectively. These were not statistically significant for different therapeutic modalities (p ⬎ 0.05). Rades et al showed that complete resection was superior to incomplete resection with statistical significance at 1-, 2-, 3-, and 4-year follow-up intervals (p ⬍ 0.05). Incomplete resection with radiotherapy was superior to the incomplete resection alone at 2-year follow-up (p ⬍ 0.05). The survival rates related to different therapeutic approaches were not statistically significant (p ⬎ 0.47) [52]. PROGNOSIS Meningeal melanocytomas have a much better prognosis than their malignant counterparts. However remote, the possibility of malignant change must be remembered. Accordingly, a maximal effort at tumor resection should be made, with expectations of a good postoperative outcome, and patients with this tumor should be followed closely. Complete tumor resection is the best therapeutic option, followed by incomplete resection combined with postoperative radiotherapy or stereotactic radiosurgery. The authors thank Drs Seyyed Mohammad Naser Hoseini and Mahnaz Banihashemi, dermatologists of the Khatam Hospital and Drs PV Kumar and Ahmad Monabbati, pathologists of Shiraz University and Elizabeth Tyler-Kabra, senior resident of neurosurgery at University of Pittsburgh for her careful review of manuscript.

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Forecast. The U.S. seems to have a frenzied passion for emulating the blunders of Great Britain. I assume that government tax-paid medical care will be no exception. A great many good doctors have left the British Isles, and people are obliged to look to Indians, Palestinians, Jamaicans, and other colonials for their medical care. Americans will have no place to go, except outside the profession. Early retirement will be the rule, and many will be locked into administrative jobs. Charles Pavey, M.D., Columbus, OH, c. 1957

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eaping the Consequences. Much of Medicare was originally designed by doctors and hospitals to feather their own nests. Now the Medicare Frankenstein has turned on them with price controls, onerous restrictions, and prosecutions. Craig Cantoni, Scottsdale, AZ

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—AAPS News, December 2002