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PubMed2000

Topical mitomycin chemotherapy for conjunctival malignant melanoma and primary acquired melanosis with atypia: clinical experience with histopathologic observations.

OBJECTIVES: To clinically evaluate topical mitomycin chemotherapy in patients with diffuse, multifocal, or recurrent primary acquired melanosis with atypia and/or conjunctival malignant melanoma and to histopathologically study ocular tissue samples obtained before and after treatment. METHODS: Chemotherapy with topical mitomycin, 0.04% 4 times daily, was administered for 28 days as the primary and only treatment in 7 patients (after biopsy) and for 7 days as adjuvant therapy to excision and cryotherapy in 5 patients. Mean follow-up was 38 months. Five patients developed subconjunctival recurrences, for which 2 underwent orbital exenteration and 3 were treated conservatively. Histopathologic specimens of conjunctival, adnexal, and ocular tissues obtained before and after chemotherapy were evaluated. RESULTS: Regression of tumor was observed in 11 patients with primary or adjuvant topical mitomycin chemotherapy. One patient with nodular melanoma was resistant to mitomycin chemotherapy. Histopathologic findings included regionally variable conjunctival epithelial atrophy and thinning. Dyskeratosis and focal keratinization in conjunctival epithelium were noted. Epithelial nuclei were occasionally pyknotic in areas of atrophic epithelium. Subepithelial inflammation was present and was most intense in areas with severe atrophy and/or keratosis. Two patients with primary treatment and 2 with adjuvant treatment developed subconjunctival recurrence. In patients with recurrent malignant melanoma, the deeper layers of the lamina propria were involved, with sparing of the epithelium and superficial lamina propria. Transient keratoconjunctivitis was observed in all patients during treatment. In evaluation of the exenteration specimens, corneal, scleral, episcleral, retinal, and anterior structures were within normal limits. CONCLUSIONS: Topical mitomycin chemotherapy was found to induce regression of conjunctival melanoma and primary acquired melanosis with atypia. When mitomycin chemotherapy was used as an adjuvant to excision and cryotherapy, 2 (40%) of 5 patients experienced tumor recurrence at a mean of 4.3 years' follow-up. Our histopathologic findings demonstrated a long-term mitomycin chemotherapy-related effect on the conjunctiva. The degree of chronic atrophy and inflammation was not clinically significant. The pattern of effect and location of recurrent disease suggest that this regimen of topical mitomycin chemotherapy was most effective for superficial tumors. No complications that would preclude use of our dose regimen were noted. Although subconjunctival or orbital recurrences were noted, topical mitomycin chemotherapy warrants further investigation as an alternative treatment for primary acquired melanosis with atypia and conjunctival malignant melanoma. Arch Ophthalmol. 2000;118:885-891

Administration, Topical↗
PubMed1975

[Melanosis coli(author's transl)].

Melanosis coli is caused by deposits of malanin- or lipofuscin-containing pigments in the colon mucosa; it is a conspicuous sign of long standing abuse of anthrachinonic laxatives. Melanosis coli can be easily diagnosed during rectoscopy, using morphological as well as histological criteria; nevertheless this condition is often overlooked or goes unnoticed. Abuse of laxatives, which is denied or concealed rather often by patients, does however explain in many cases otherwise unexplained abdominal complaints. Four cases are reported demonstrating the diagnostic significance of colonic melanosis.

Adult↗
PubMed2003

[Melanocytic meningitis and large congenital melanocytic naevus: neurocutaneous melanosis].

Neurological symptoms in a patient with large congenital melanocytic naevus are highly suggestive of cerebromeningeal melanoma metastasis. The presence of melanocytic cells in cerebrospinal fluid confirms this diagnosis If their malignant nature is shared with cutaneous naevocytic cells. Conversely, neurocutaneous melanosis is diagnosed when benign melanocytosis meningitis is found in patients with multiple and/or large congenital melanocytic naevus, whether cutaneous naevus cells are benign or not, or when cerebrospinal fluid cells are malignant with benign cutaneous melanocytic naevus. We report the case of a young man aged 19 presenting with multiple and large congenital melanocytic naevus who experienced transcient neurological signs and increased intracranial pressure. Cerebral neuroimaging evoked meningeal infiltration which benign melanocytic nature was supposed on CSF analysis and confirmed by necropsy findings, only 3 month after neurological onset, leading to neurocutaneous melanosis diagnosis. This rare neuroectodermal dysembryoplasia finds expression in various neurological signs, depending on patient's age and leptomeningeal and/or cerebral proliferation localization. Lumbar puncture, cerebral scanography and MRI may help diagnosis, but only histological examination can prove neurocutaneous melanosis, more often by necropsy because of poor prognosis.

Adult↗
PubMed2005

[Conjunctival primary acquired melanosis].

BACKGROUND: Pigmented lesions of the conjunctiva may represent primary acquired melanosis. If histological examination reveals atypical melanocytes in the epithelial layer of the conjunctiva, there is a close to 50% risk of transformation to a conjunctival malignant melanoma. A combination of surgical excision and cryotherapy is the most widely recommended treatment for conjunctival primary acquired melanosis with atypia. Recently, topical chemotherapy with mitomycin-C eye drops has been established as a therapeutic option. MATERIAL AND METHODS: Based on two case reports and a review of the literature, clinical aspects and the use of topical chemotherapy are presented. RESULTS AND INTERPRETATION: Pigmented conjunctival lesions arising in adults may represent primary acquired melanosis with atypia. In patients with large or multiple pigmentations, extensive surgery with cryotherapy is necessary. In such circumstances, topical chemotherapy with mitomycin-C eye drops is a good alternative and may lead to complete regression, as in our two patients.

Aged↗
PubMed1989

[Primary malignant melanoma of the esophagus arising in melanosis. Histological, immunohistochemical and ultrastructural study of a case].

The authors report a case of a primary melanoma of the esophagus, which is a rare neoplasm with poor prognosis. The diagnosis of malignant melanoma was suggested, on endoscopic biopsies, because of the presence of large malignant cells with abundant cytoplasm containing melanin pigment positive in the Fontana-Masson's reaction. These cells were immunoreactive for S100 protein while they did not show staining for antiepithelial membrane antigen and anti-keratin antibodies. Moreover ultrastructural study of the tumor cells revealed cytoplasmic aberrant premelanosomas. An important histological feature of the present case, which confirmed the primary oesophageal nature of the tumor was the presence of foci of melanosis (benign melanocytes) within the oesophageal epithelium which was adjacent to the melanoma. The variation in the histology of malignant melanoma may provide difficulties in diagnosis especially if one is limited to study a small biopsy specimen. In such cases other diagnoses including epidermoid carcinoma with prominent spindle-cell features and sarcomas should be eliminated by means of immunohistochemical and ultrastructural studies. The particular feature of our case, which apparently has not been reported previously, is the identification of the melanosis two years prior to the diagnosis of the malignant melanoma. The present study indicates that the identification of this lesion is of important diagnostic interest and might lead to the follow-up surveillance of the melanosis by multiple biopsies.

Esophageal Neoplasms↗
PubMed1985

Open angle glaucoma in melanosis oculi: response to laser trabeculoplasty.

The case for an association between secondary open angle glaucoma and melanosis oculi is strengthened by our recent observation of a teenaged male with advanced glaucomatous damage in the eye with melanosis oculi. This report summarizes his clinical findings, his response to medical therapy and laser trabeculoplasty, and suggests the possibility that melanosis oculi causes secondary open angle glaucoma in patients who are predisposed to primary open angle glaucoma.

Adolescent↗
PubMed1979

[Malignant melanoma of the choroid in melanosis bulbi (author's transl)].

Report of a case with melanosis bulbi observed in a relatively young patient of 33 years, in which a malignant melanoma of the choroid developed. As reported in earlier examinations the incidence of malignant melanoma in cases of melanosis bulbi is much higher than in normal eyes. The authors recommend strongly routine biomicroscopic examinations in cases of melanosis bulbi every 1--2 years to recognize the development of a melanoma in an early stage.

Adult↗
PubMed1978

[Colonic melanosis].

Among 1072 rectoscopies we found 100 patients (9,3%) with melanosis coli. All patients suffered from a long-standing constipation together with laxative abuse. Anthrachinonic laxatives which are jointly responsible for the cause of melanosis coli are contained in 70% of all laxatives but also in many cholagogues and weight-reducing preparations. Severe inflammation of the colonic mucosa was seldom found. Colitis simplex, often found histologically and cytologically, could be due to increased turn-over of the mucosa cells. The endoscopic finding of melanosis coli is not regarded as an independent clinical picture but as an expression of chronic constipation unsuccessfully treated with laxatives.

Aged↗
PubMed1982

[Reese's conjunctival melanosis. Two anatomicoclinical observations with ultrastructural study in one case].

Two cases of Reese's conjunctival melanosis are reported. Inflammatory signs revealed the presence of the lesion in a 58-year-old woman, examination demonstrating diffuse brown conjunctival, tarsal, and bulbar pigmentation in the right eye, raised above the surface at the sclerocorneal junction. Histology after exenteration demonstrated coexisting diffuse atypical melanocytic hyperplasia (precancerous melanosis), an intraepithelial melanoma (cancerous melanosis), and an invasive melanoma which was the object of an ultrastructural study. The second case, a 57-year-old woman, had a 20-year history of stable, diffuse black pigmentation of the bulbar conjunctiva of the right eye. Four months after biopsy, a pedunculated tumor of the internal canthus developed, corresponding to a poorly differentiated epithelioid cell malignant melanoma. These two cases are compared with similar observations reported in the literature.

Adult↗
PubMed1980

"Melanosis" of the duodenum associated with a gastric ulcer and folic acid deficiency.

Melanosis involving the duodenum is extremely rare. We present endoscopic, microscopic, and histochemical studies of a patient with melanosis of the duodenum associated with a gastric ulcer and a folic acid deficiency. The pigment is similar to that observed in melanosis coli and histochemically does not stain like melanin or lipofuscin. The pigment disappeared with correction of the folate deficiency and healing of the gastric ulcer, suggesting a possible relationship with these entities.

Aged↗
PubMed1994

[Neurocutaneous melanosis--a case report].

Neurocutaneous melanosis is a rare congenital phacomatosis characterized by the presence of large or multiple congenital melanocytic nevi and benign or malignant pigmented cell tumors of the leptomeninges. A 14-month-old boy was admitted with a recent history of vomiting and drowsiness. He was found to have multiple congenital melanocytic nevi. Gd-enhanced MRI showed ventriculomegaly and leptomeningeal enhancement in the ambient cistern. CSF cytology revealed abnormal cells with pigmented granules. A diagnosis of hydrocephalus with malignant neurocutaneous melanosis was made. The patient was treated with combination chemotherapy (DAV therapy, ACNU intrathecal perfusion therapy, interferon beta therapy) while controlling intracranial pressure by CSF drainage, but in spite of treatment he died due to rapid progression of leptomeningeal infiltration. Postmortem examination revealed meningeal malignant melanomas predominantly at the base of the brain and benign meningeal melanosis over the cerebral cortex. Newborn infants or infants with large or multiple congenital melanocytic nevi should be carefully followed, especially for the first two years. When hydrocephalus or convulsions occur in patients with skin lesions, Cd-enhanced-MRI and careful CSF cytology studies should be performed to detect meningeal abnormalities.

Humans↗
PubMed1993

[A case of Duane's syndrome with ocular melanosis].

Duane's syndrome has various ocular and systemic abnormalities. We report a Duane's syndrome patient with ocular melanosis. Duane's syndrome has many complications, but ocular melanosis has never been reported previously. It is possible that there is a similar mechanism between the ocular melanosis and misdirection of the oculomotor nerve to the external rectus in this case, but it is more probable that it is simply coincidental.

Child↗
PubMed1977

[Does a circumscribed melanosis secondary to malignant melanoma exist?].

Regarding the rare phenomenon of diffuse melanosis of the skin secondary to widespread melanoma, the possibility of a circumscribed melanosis in melanoma patients is hypothetically discussed on the basis of a personal observation. Microscopically, such a circumscribed melanosis appears as clusters of melanin-laden macrophages.

Humans↗
PubMed1997

Malignant melanoma of the lacrimal sac with surrounding melanosis.

Primary malignant melanomas of the lacrimal sac are extremely rare. In this report, the histologic findings of primary malignant melanoma of the lacrimal sac with surrounding melanosis are presented. Histologically, the surrounding melanosis showed radial proliferation of atypical melanocytes along the mucosal epithelium. Although we came to no firm conclusion as to whether the malignant melanoma in the present case was preceded by melanosis (radial proliferation of atypical melanocytes), to our knowledge this is the first description of lacrimal sac malignant melanoma associated with a lesion of this kind in the surrounding epithelium.

Cell Division↗
PubMed1997

MR imaging of symptomatic neurocutaneous melanosis in children.

Neurocutaneous melanosis is a syndrome consisting of cutaneous nevi and melanocytosis of the leptomeninges. Over a 5-year period (1989-1994) we evaluated with MR imaging the central nervous system of five children with a confirmed histologic diagnosis of neurocutaneous melanosis. The children ranged in age from 7 to 10 years and consisted of two girls and three boys. They all had multiple pigmented skin lesions (cutaneous nevi) and presented with seizures, signs of raised intracranial pressure, cranial nerve palsies and/or myelopathy. The MR studies were performed with T1-weighted, T2-weighted and T1-weighted post-gadolinium images of the brain in addition to T1-weighted post-gadolinium images of the entire spine. The MR findings in all the children consisted of marked, diffuse enhancement of thickened leptomeninges surrounding the brain and spinal cord which was only demonstrated on the post-gadolinium T1-weighted images and mild to moderate hydrocephalus. We present our MR findings and compare these findings with other imaging findings in the literature. Our findings represent part of a spectrum of imaging abnormalities seen in patients with neurocutaneous melanosis.

Brain↗
PubMed2002

Histological, immunological and molecular features of a nasal mucosa primary melanoma associated with nasal melanosis.

Nasal mucosa melanoma is a rare entity that may occur together with nasal melanosis. The histological and immunological features and loss of heterozygosity analysis of such lesions have not been reported to date. In the study presented here short-term cell cultures were established from the patient's melanoma and subsequent relapses. Histology, immunohistochemistry, reverse transcription-polymerase chain reaction enzyme-linked immunosorbent assay, human leukocyte antigen analysis, microdissection with subsequent polymerase chain reaction for analysis of loss of heterozygosity were used to characterize the tumour and other cells. Melanoma of the nasal cavity was found, with a surrounding proliferation of atypical melanocytes corresponding to nasal melanosis. Immunoreactivity was found for S-100, gp100, tyrosinase and MelanA protein. Loss of heterozygosity for a p16-flanking marker was found in the tumour and the melanotic cells. Short-term cell cultures expressed tyrosinase and MUC18 at the mRNA level and intercellular adhesion molecule-1 (ICAM-1) and interleukin-12 receptor at the protein level. This is the first time short-term cell cultures have been established and analysed from such a tumour. Melanoma-associated antigens were identified within the tumour. The melanoma and the melanotic cells showed loss of heterozygosity for the p16 gene, which is implicated in melanoma development. This points to a common origin in tumorigenesis. Pathways of tumour escape, such as expression of CD54 and interleukin-10, were observed. The clinical, immunological and molecular features suggest that nasal melanosis should be followed closely.

Adult↗
PubMed2004

Neurocutaneous melanosis associated with Dandy-Walker malformation and a meningohydroencephalocele. Case report.

Neurocutaneous melanosis and Dandy-Walker malformation are both forms of rare congenital neurodysplasia. Interestingly, 8 to 10% of patients with neurocutaneous melanosis also harbor an associated Dandy-Walker malformation, indicating that these developmental abnormalities share a common origin. The authors describe a case of neurocutaneous melanosis associated with Dandy-Walker malformation and an occipital meningohydroencephalocele with a giant melanotic nevus. Multiple congenital liver masses were also observed in the infant. The occipital nevus was totally excised, and ventriculoperitoneal and cyst-peritoneal shunts were created to prevent subsequent hydrocephalus. Findings in this case support the possibility that excessive melanocytes hinder normal mesenchymal development, causing Dandy-Walker malformation and an occipital meningocele.

Dandy-Walker Syndrome↗
PubMed1987

[An autopsy case of neurocutaneous melanosis associated with intracerebral malignant melanoma].

The authors reported the clinical course and the postmortem examination of a unique case of neurocutaneous melanosis with numerous anomalies and complications, which included congenital dislocation of lenses, hypogonadism, ectopia of prostatic duct, genuine phimose, retentio testis, psina bifida and neurogenic bladder. This 13-year-old boy with a large hairy nevus in a bathing trunk configulation and multiple small nevi over the whole body since his birth was admitted to our hospital for evaluation of headache and vomiting. Neurological examination showed bilateral papilledema and slight left hemiparesis. A CT scan revealed a large right frontal mass and craniotomy was performed with subtotal removal of this tumor which was confirmed as a malignant leptomeningeal melanoma. He initially made uneventful postoperative recovery, and two courses of chemotherapy with DTIC, ACNU and VCR were given; however, the currence of brain tumor ensued shortly thereafter, and he died in approximately six months after the onset of intracranial symptoms despite of the third course of chemotherapy. Thirty five cases of neurocutaneous melanosis associated with or without malignant melanoma have been reported in Japan. Twenty-eight cases were male and 7 female. Two cases showed the evidence of primary malignant melanoma outside of the central nervous system, whereas twenty eight leptomeningeal melanoma, in which 22 were solid and 6 diffuse, were shown intracranially. Other 5 cases had epileptic seizure and/or hydrocephalus caused by wide spreaded leptmeningeal melanosis. This high incidence of intracranial malignant melanoma in this disorder was remarkable compaired with the previous reports in other countries. Mean duration between deaths and the onset of symptoms of intracranial hypertension or focal neurological signs was 7 months, ranging from 1 to 24 months, showing the rapidly deteriorating course in this disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗