Topical interferon alfa in the treatment of conjunctival melanoma and primary acquired melanosis complex

PURPOSE: To report on topical interferon alfa-2b for conjunctival malignant melanoma (CMM) and primary acquired melanosis with atypia (PAM). DESIGN: Retrospective, interventional case series. METHODS: Five eyes of five consecutive patients with biopsy-proven malignant melanoma were treated with topical interferon alfa-2b as treatment for primary or recurrent disease. One drop of interferon alfa-2b (1 million units/ml) was placed into the superior fornix four times daily for three months. Punctal plugs limited systemic absorption. The main outcome measure was tumor regression by clinical examination and comparative slit-lamp photography. RESULTS: Five consecutive patients with conjunctival melanoma (American Joint Committee on Cancer-International Union Against Cancer stages T2 [n = 3] and T3 [n = 2]) were included. Two patients had recurrent corneal tumors, eight and 13 months after local excision, cryotherapy, and topical mitomycin C therapy. Two months after topical interferon alfa-2b treatment, the lesions regressed without side effects. Two additional patients (who could not tolerate topical mitomycin C) were switched to topical interferon alfa-2b. They experienced transient chemical conjunctivitis and have no signs of recurrence (mean, 15 months of follow-up). The fifth had recurrent tumor despite multiple surgeries. This melanoma did not respond to topical interferon alfa-2b nor did the patient tolerate treatment (keratoconjunctivitis). No systemic side effects were noted. CONCLUSIONS: We present evidence that conjunctival and corneal melanoma regresses after exposure to topical interferon alfa-2b. A larger-scale longer-term study must evaluate the long-term efficacy and safety of this therapy.     

Intumescent cataract after topical mitomycin-C for conjunctival malignant melanoma

PURPOSE: To present the clinical and histologic findings of a patient in whom intumescent cataract developed after successful topical mitomycin-C (MMC) chemotherapy for conjunctival melanoma originating from primary acquired conjunctival melanosis (PAM) with atypia. DESIGN: Observational case report; follow-up at 30 months. METHODS: In a patient with PAM and subsequent conjunctival melanoma that was successfully treated with topical MMC chemotherapy an intumescent cataract developed after two cycles of 0.04% MMC, each for 1 month. RESULTS: After MMC chemotherapy pigmentation of the acquired melanosis vanished almost completely. Histopathology of the check-up specimen revealed local tumor control. Six weeks after the completion of the second cycle, an intumescent cataract developed. Cataract surgery was performed uneventfully. The patient was followed up for 30 months. CONCLUSIONS: In selected cases, topical MMC chemotherapy is effective for treating conjunctival melanoma. Although severe complications are rare and usually transient, development of cataract may be observed. A prospective study should be initiated.     

Treatment of conjunctival papillomata with topical interferon Alfa-2b

PURPOSE: Two patients with biopsy-proven conjunctival papillomata exhibited complete resolution after treatment with topical Interferon Alfa-2b (IFNalpha2b). DESIGN: Interventional case reports. METHODS: Two patients with monocular biopsy-confirmed conjunctival papillomata were treated with IFNalpha2b, 1 million units/cc, one drop four times daily until clinical resolution was achieved. RESULTS: (Patient 1) The lesion's size was significantly reduced at 1 month. Complete resolution was noted at the 3-month visit. No recurrences were seen 40 months post-treatment. (Patient 2) The lesion completely resolved after 6 weeks of treatment. No recurrence has occurred 18 months post-treatment. No systemic or local side effect of treatment was noted. CONCLUSIONS: Two sizable conjunctival papillomata resolved using topical IFNalpha2b alone. Interferon is usually not considered effective for large solid tumors without surgical debulking. We realize that this is a limited case series, but these cases may serve as a basis for further investigation.     

Topical mitomycin C in the treatment of pigmented conjunctival lesions

PURPOSE: To assess the clinical efficacy of topical mitomycin C (MMC) 0.04% for the treatment of patients with pigmented conjunctival lesions. Clinical efficacy was evaluated on the basis of reduction in lesion size and degree of pigmentation and histologic study. METHODS: Two patients, one with primary acquired conjunctival melanosis with atypia and another with conjunctival melanoma, were treated with topical MMC 0.04%. Before treatment, a biopsy was performed that confirmed the diagnosis and the absence of atypical melanocytes beyond the basal layer. In both patients, MMC was administered with sponges, while one patient additionally received MMC 0.04% drops. Each treatment cycle lasted 14 days, with repetition after 3 months when necessary. Follow-up was weekly, then monthly, and then every 6 months up to 3 years. RESULTS: Treatment with topical MMC 0.04% not only reduced the size and degree of pigmentation clinical lesions in both patients but also eradicated atypical conjunctival melanocytes as observed in histologic studies. In the patient with primary acquired conjunctival melanosis, adjunct cryotherapy was required, along with various cycles of MMC, to reduce the pigmented areas of skin of the internal canthus and caruncle. In the second case, only MMC was used. No severe adverse reactions to the treatment were observed. After 3 years of follow-up, no clinical relapse has been detected. CONCLUSION: Topical MMC 0.04% is an option worth considering for the treatment of pigmented conjunctival lesions, particularly as an adjunct to other forms of treatment.     

Perilesional and topical interferon alfa-2b for conjunctival and corneal neoplasia

ObjectiveTo evaluate the role of combined subconjunctival and topical interferon alfa-2b (IFNα2b) in the treatment of conjunctival and corneal intraepithelial neoplasia (CIN).DesignNoncomparative case series.ParticipantsSix patients with histologically proven CIN or recurrences of histologically proven CIN were studied prospectively.InterventionPatients were given a single subconjunctival/perilesional injection of recombinant IFNα2b (Schering Plough, Kenilworth, NJ) 3 million international units (IU) in 0.5 ml and then started receiving topical interferon drops (1 million U/ml) four times a day. Patients were followed weekly until complete resolution of the tumor. After 1 week, patients with minimal response while receiving topical therapy were retreated with perilesional injections three times a week until resolution. Patients received topical interferon drops for a month after clinical resolution of the lesion.Main outcome measuresPatients were followed clinically and photographically for evidence of tumor resolution.ResultsThe authors present a series of six patients who were treated successfully with a combination of subconjunctival/perilesional and topical IFNα2b. All six patients had complete clinical resolution of the CIN lesion within 6 weeks of initiation of treatment. In the time of follow-up (average, 7.2 months; range, 2–11 months), there have been no treatment failures or recurrences.ConclusionIFNα2b may be a viable medical alternative to surgical excision for primary or recurrent CIN.     

Animal model of conjunctival primary acquired melanosis

A condition clinically identical to human conjunctival primary acquired melanosis (PAM) was induced in 16 of 20 Dutch (pigmented) rabbits after weekly topical 60-microliters applications of a 1% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in acetone. Pigment stippling appeared in the conjunctiva as early as 5 weeks after the initial carcinogen application. Confluent patches of flat pigmentation appeared over the palpebral conjunctiva 18 weeks after the onset of treatment and showed progressive lateral enlargement and darkening. Histologically, a spectrum of changes from increased melanin production and melanocytic hyperplasia without atypia (resembling the human condition of PAM without atypia) through atypical melanocytic hyperplasia (resembling human PAM with atypia) was identified. The development of this model permits further investigations to explore and explain the clinically observed phenomenon of waxing and waning of PAM and its promotion to conjunctival malignant melanoma.     

Amniotic membrane transplantation in the management of conjunctival malignant melanoma and primary acquired melanosis with atypia

AIM: To evaluate the efficacy of amniotic membrane transplantation (AMT) for the management of conjunctival malignant melanoma and primary acquired melanosis (PAM) with atypia. METHODS: Four consecutive patients with histologically proved invasive, primary conjunctival malignant melanoma were treated with wide surgical excision and AMT. Amniotic membrane grafts were harvested and processed under sterile conditions according to a standard protocol. The grafts were sutured to the margins of the surface defect. In one case, AMT was combined with a corneoscleral graft. RESULTS: A satisfactory result and rapid postoperative recovery with few, transient side effects was noted in three patients with limbal/epibulbar melanomas. In another patient with an extensive lesion, involving the epibulbar, forniceal, and palpebral conjunctiva, AMT following wide excision was complicated by symblepharon formation and restricted ocular motility. Monitoring of local recurrence was facilitated by the transparency of the thin graft in all cases. The postoperative follow up time varied between several months and 3 years. In one case, local recurrence of PAM was observed and treated using topical mitomycin. CONCLUSIONS: AMT is a useful technique for the reconstruction of both small and large surface defects that result from the surgical excision of conjunctival malignant melanoma and PAM. This method facilitates wide conjunctivectomy, although its role in repairing larger defects involving the fornix or palpebral conjunctiva still needs to be established. The transparency of amniotic membrane allows for monitoring of tumour recurrence, which is-together with superior cosmesis-an advantage over thicker (for example, buccal) mucous membrane grafts.     

Topical mitomycin C chemotherapy for conjunctival melanoma and PAM with atypia

AIM—To evaluate topical mitomycin C (MMC) chemotherapy in the treatment of conjunctival melanoma and primary acquired melanosis with atypia.
METHODS—In a phase I clinical trial, 10 patients with conjunctival melanoma and/or primary acquired melanosis with atypia were treated with topical MMC 0.04% four times daily. Four patients were given MMC for 28 days as a primary treatment. Six patients were treated with MMC for 7 days after excision and cryotherapy in an effort to improve local control. In this series, 10 patients have been followed for an average of 29 months.
RESULTS—All patients were noted to develop transient keratoconjunctivitis during treatment. One patient also developed a transient corneal epithelial defect. Decreased conjunctival pigmentation was noted in the four patients where topical chemotherapy was used as a primary treatment. Nodular tumours were resistant to topical MMC chemotherapy. Of the six patients treated within 2 weeks after primary excision and cryotherapy, there has been no tumour recurrence or symblepharon formation. Nine of the 10 study patients have maintained within one line of their pretreatment visual acuity. No retinal or optic nerve toxicity was noted.
CONCLUSION—Since no complications which might preclude further investigation of topical MMC chemotherapy occurred, it was concluded that topical MMC chemotherapy was tolerated as a treatment for conjunctival melanoma and primary acquired melanosis with atypia.

Keywords: conjunctival melanoma; primary acquired melanosis; mitomycin C     

The treatment of primary acquired melanosis (PAM) with atypia by topical Mitomycin C

PURPOSE: To report our results of 12 consecutive patients with conjunctival primary acquired melanosis (PAM) with atypia who were treated by topical Mitomycin C (MMC). DESIGN: Retrospective interventional consecutive case series. METHODS: Twelve patients with PAM with atypia in one of their eyes who were treated by topical chemotherapy with MMC were included in this case study. Eyes with histologically proven PAM with atypia were treated by two to five courses of 0.04% (0.4 mg/ml) MMC four times a day. Each course lasted 2 continuous weeks. Follow-up was conducted on patients for control of local disease, side effects, and visual acuity in the treated eye. RESULTS: In all patients, there was complete or partial response to treatment. In four patients, the pigmentation disappeared, whereas in eight patients, some remnants of the pigmentation remained. In seven of these eight patients, the remnants of the pigmentation were stable during the follow-up period of 4 months to 9 years, whereas one in whom re-growth of the PAM was noticed was successfully treated again by topical MMC. No patients lost visual acuity at the end of the follow-up. All side effects of the local chemotherapy were resolved after cessation of the treatment. CONCLUSIONS: Topical MMC chemotherapy is a good alternative to surgical excision and cryotherapy in treating conjunctival PAM with atypia.     

Conjunctival melanoma arising from diffuse primary acquired melanosis in a young black woman

PURPOSE: To report a case of conjunctival melanoma arising from diffuse primary acquired melanosis (PAM) with atypia in a young black woman in the context of previously published cases of this lesion in blacks. METHODS: Retrospective case report with literature review. The number and percentage of conjunctival melanomas occurring in black patients were determined from case series in which race was specified, published from 1950 to the present. RESULTS: Nodular multifocal conjunctival melanoma in a 30-year-old black woman was treated using surgical excision and adjuvant cryotherapy. Extensive PAM with severe atypia, including areas of microinvasive melanoma, was treated using topical mitomycin C. Literature review revealed 35 cases of conjunctival melanoma occurring in black patients. No previous reports of mitomycin C use in black patients with melanoma or PAM were identified. CONCLUSIONS: Conjunctival melanoma is an exceedingly rare tumor in black patients. The current case brings the total of reported cases to 36. We successfully treated nodular melanoma and diffuse PAM in a young black woman using a combination of excision with cryotherapy and topical mitomycin C, suggesting that these lesions are amenable to the same types of therapy previously described for white patients.     

Resolución de un melanoma conjuntival con interferón tópico alfa 2 b en un paciente con intolerancia a la mitomicina C

Objective

To describe the clinical and histological resolution of a case of an inexcisable conjunctival melanoma using topical interferon alpha 2 b (INFα2b) in a patient with mitomycin C (MMC) intolerance.

Primary acquired melanosis of the conjunctiva.

BACKGROUND: Primary acquired melanosis (PAM) presents as a unilateral patchy area of conjunctival pigmentation mostly found in middle-aged or elderly white patients. Because PAM has the potential of becoming malignant, it is important to recognize PAM and to rule out other causes of pigmented lesions. The presence or absence of atypia is helpful in determining the potential for malignancy, because PAM without atypia is usually benign, whereas PAM with atypia may convert into a conjunctival melanoma. If atypia is present, the presence or absence of epithelioid cells and the pattern of intraepithelial growth are the main factors in determining the likelihood of neoplastic transformation. However, atypia can only be determined with histopathologic examination. Therefore, a biopsy is usually recommended. CASE REPORT: A 72-year-old white man presented for his annual examination with no visual complaints. His ocular history was remarkable for early cataracts and for a choroidal nevus. Slit lamp examination found a large dark area of elevated conjunctival pigmentation at the medial canthus that extended onto the superior bulbar conjunctiva and superior palpebral conjunctiva in the left eye. No conjunctival pigmentation had been noted previously. Results of a biopsy indicated primary acquired melanosis with atypia. The lesion was surgically excised, and the conjunctiva was reconstructed with an amniotic membrane graft. The patient was subsequently treated with topical 5-fluorouracil chemotherapy. There have been no signs of recurrence to date after his treatment. CONCLUSION: Because of the potential for malignancy, biopsies of all cases of primary acquired melanosis are indicated. If atypia is present, treatment options include local excision, cryotherapy, and topical chemotherapy.     

Topical mitomycin-C for partially excised conjunctival squamous cell carcinoma

PURPOSE: To evaluate the efficacy of topical mitomycin-C (MMC) for treatment of postoperative residual conjunctival squamous cell carcinoma (SCC). DESIGN: Retrospective noncomparative case series. PARTICIPANTS: Five patients, two males and three females, with conjunctival and histologically proven incompletely excised conjunctival SCC. METHODS: Patients were treated with topical MMC. Two to three courses of topical MMC, 0.02% or 0.04%, were applied four times daily for 14 days per course. One month after the final treatment, the scar area with surrounding normal conjunctiva was excised, and histologic evaluation was done. MAIN OUTCOME MEASURES: No evidence of malignant cells in excised tissues. RESULTS: Histologic evaluation of the five specimens showed no malignant cells. Conjunctival scarring with inflammatory response was observed. No regrowth was reported during the follow-up period of 18 to 37 months. The complications of MMC use included mild to moderate conjunctival hyperemia in three patients. All signs and symptoms were resolved after discontinuation of the treatment. CONCLUSIONS: Application of topical MMC is an efficient treatment for residual conjunctival SCC. Longer follow-up is required to confirm these findings.     

Treatment of conjunctival squamous cell carcinoma with topical 5-fluorouracil

AIM: To evaluate the efficacy of topical 5-fluorouracil (5-FU) alone, without concurrent surgery or radiotherapy, for the treatment of conjunctival squamous cell carcinoma. METHODS: Eight patients affected by conjunctival squamous cell carcinoma (three recurrent cases, three incompletely excised, and two untreated cases) were treated with 1% 5-FU eye drops. Topical 1% 5-FU was administered four times daily for 4 weeks (one course). Clinical examination (biomicroscopy and photography) and morphological evaluation of conjunctival cytological specimens were used to monitor the efficacy of local chemotherapy, side effects, and recurrences. RESULTS: All patients showed clinical regression of conjunctival carcinoma after topical 1% 5-FU treatment. Neoplastic conjunctiva was completely replaced by normal epithelium within 3 months. Mean follow up was 27 months. One patient needed two courses of local chemotherapy for recurrent disease. An acute transient toxic keratoconjunctivitis was observed in all treated cases; it was easily controlled with topical therapy. No long term side effects were found. CONCLUSIONS: Topical 1% 5-FU is effective in the treatment of recurrent, incompletely excised, and selected untreated conjunctival squamous cell carcinomas. Topical 1% 5-FU has no major complications. This study suggests that topical conjunctival chemotherapy with 1% 5-FU may be useful, at least as adjunctive therapy, in the treatment of conjunctival squamous cell carcinoma.     

Regression of presumed primary conjunctival and corneal intraepithelial neoplasia with topical interferon alpha-2b.

PURPOSE: To evaluate topical interferon alpha-2b (IFNalpha2b) as a lone therapy in the treatment of primary conjunctival and corneal intraepithelial neoplasia (CIN). METHODS: Noncomparative, prospective, interventional case series. Seven patients from three institutions, treated between February and October 1999, with presumed primary CIN lesions (clinically diagnosed by corneal specialists) were given topical IFNalpha2b drops (1 million units/mL) four to six times daily. Follow-up was performed biweekly until there was complete clinical resolution of the presumed CIN lesions. Patients were to continue topical IFNalpha2b drops for 1 month after clinical resolution. Patient charts and clinical photographs were reviewed, and data were analyzed. RESULTS: All seven eyes had complete resolution of the presumed CIN lesions after an average of 77.0 +/- 59.2 days (range, 28-188 days). Average posttreatment follow up was 12.4 +/- 2.5 months (range, 9-16 months). No patients were lost to follow-up. No recurrences have yet been seen. Side effects of treatment were limited to mild conjunctival hyperemia and follicular conjunctivitis in four (57.1%) eyes. In all cases, there was total resolution of conjunctival hyperemia and follicular changes within 1 month after cessation of the medication, without additional treatment. CONCLUSIONS: Topical IFNalpha2b alone may be an effective treatment of primary CIN. It appears to be a safe alternative to radiation, intralesional IFNalpha2b injection, and surgical excision with cryotherapy. Larger population studies with longer follow-up are recommended to better assess the risk of recurrence and other possible adverse effects.     

Topical mitomycin chemotherapy for conjunctival malignant melanoma and primary acquired melanosis with atypia: 12 years’ experience

Purpose To report 12-year follow-up experience with topical mitomycin chemotherapy for diffuse and multifocal primary acquired melanosis (PAM) with atypia and conjunctival melanoma. Methods Interventional case series of 16 patients. Mitomycin was a primary treatment for residual epithelial disease in ten patients (eight with PAM with atypia and two with conjunctival melanoma) and as an adjuvant to excision and cryotherapy in six with conjunctival malignant melanoma. Primary treatments consisted of mitomycin 0.04% qid for 28 days (two 14-day cycles) and for 7 consecutive days as adjuvant therapy. Patients were followed for both local recurrence and metastatic disease. Results Sixteen patients were followed for a mean 81 months (range 13–144 months) after treatment. All tumors responded to chemotherapy. Recurrence was noted in eight (three adjuvant and five primary treatment patients). Three underwent orbital exenteration. The remaining five were treated conservatively. The mean time to recurrence was 36.9 months. The short-term mitomycin-related complications included transient keratoconjunctivitis (n=14), severe keratoconjunctivitis (n=1) and one corneal abrasion with scar formation. The long-term complications included pannus (n=2) and corneal haze (n=1). Visual acuity was maintained within two lines in 14 patients (including measurements just prior to exenteration). Three patients died, one of metastatic conjunctival melanoma. Conclusions Conjunctival melanoma and PAM responded to mitomycin 0.04% topical chemotherapy; subepithelial nests appeared resistant to treatment. Treatment-related complications were acceptable. In this series, as primary and adjuvant therapy, topical mitomycin yielded an overall recurrence rate of 50%. Presented (in part) at the American Academy of Ophthalmology Annual Meeting, New Orleans, October 2004.     

Cryotherapy for conjunctival primary acquired melanosis and malignant melanoma. Experience with 62 cases

Sixty-two patients were treated by some combination of cryotherapy and surgery with an average follow-up of 3.3 years for one of the following diseases: focal or diffuse flat conjunctival primary acquired melanosis (PAM) with atypia but without a nodule of melanoma (10 cases); unifocal malignant melanoma with or without focal or diffuse PAM (30 cases); and multinodular/multicentric melanoma with and without PAM (22 cases). Of the ten patients who had PAM with atypia, invasive nodules of malignant melanoma did not develop. A second treatment was required to control the disease in four of the ten patients with extensive or diffuse lesions, and one has mild persistent disease. Of the 30 patients with unifocal nodules of malignant melanoma, 27 remained free of recurrence after one treatment, and 2 are asymptomatic after two treatments. One patient with a thick nodule at presentation required a parotidectomy and radical neck dissection for cervical metastases after recurrence in the conjunctival sac. In the group of 22 patients with multinodular malignant melanoma, only two did not have recurrent disease after one treatment. Of those who received multiple therapies, seven remained free of recurrence for at least 2 years after the last treatment; regional or distant metastases developed in nine; four required exenteration; and eight died. Conjunctival adjunctive cryotherapy avoids exenteration in extensive lesions of pure PAM and in unifocal melanoma, but even after multiple therapies, multinodular malignant melanoma had a 45% rate of metastasis. Metastasis was related to the presence of PAM sine pigmento in four patients (microscopically but not clinically detectable PAM); to the location of the nodules (9 of 10 patients who experienced metastases had forniceal, palpebral, and/or caruncular nodules); to the thickness or depth of invasion of the nodules (greater than 2 mm); and to the development of intralymphatic spread ("in-transit" local metastasis) within the conjunctival sac in six patients. No metastases were encountered among patients with strictly limbal nodules and among five patients with invasive nodules composed of spindle cells in part or in toto. Therapeutic success in this spectrum of melanocytic proliferations is closely correlated with the clinical extent of the disease when initiating definitive therapy.     

In vivo confocal microscopy of pigmented conjunctival tumors

PURPOSE: To analyze the appearance of conjunctival pigmented tumors as seen by in vivo confocal microscopy. METHODS: Twenty-eight pigmented conjunctival tumors including 6 nevi, 13 acquired melanoses, 7 conjunctival melanomas, and 2 extrascleral growths of uveal melanomas were examined by in vivo confocal microscopy using the Heidelberg Retina Tomograph (HRTII)/Rostock Cornea Modul (RCM). Confocal images were analyzed using predefined criteria by an observer masked to final histological diagnosis and a preliminary diagnosis was established. After excision, histology and immunohistochemistry using antibodies against S-100, Melan-A, HMB-45, Ki-67, CD3, and CD68 were performed in all specimens and compared with in vivo confocal images of the same lesions. RESULTS: Confocal microscopy images confirmed typical histopathological features of conjunctival pigmented tumors. Nest or diffuse collections of medium-sized uniform hyper- or hyperreflective cells in the stroma and stromal cysts lined with a multilayered epithelium were visible in 100% of conjunctival nevi. Small dendritic cells were typically observed in 100% of primary acquired melanoses (PAM) without atypia and in 2 out of 6 nevi. Large networks of hyperreflective dendritic cells were present in 100% of PAM with atypia. Whereas images of PAM without atypia and secondary complexion-associated melanosis showed hyperreflective granules confined to the basal epithelium in 67% of lesions, PAM with atypia presented with hyperreflective granules and patches throughout the epithelium in all cases. Malignant melanomas of the conjunctiva and extrascleral growths of uveal melanomas demonstrated large hyperreflective cells with prominent nuclei and nucleoli. In vivo confocal microscopy showed a sensitivity of 89% and a specificity of 100% to establish the correct diagnosis of conjunctival melanoma compared with histology. CONCLUSIONS: High correlations were found between in vivo confocal microscopy using near-infrared laser light and histology in the diagnosis of pigmented conjunctival lesions. In vivo confocal microscopy seems to be a valuable new tool in the differential diagnosis and follow-up of pigmented conjunctival tumors. It does not replace histology, but may assist in performing guided biopsy in tumors suspected clinically and/or with in vivo microscopy. In addition, in vivo confocal microscopy may support the clinical diagnosis of extrascleral involvement in uveal melanoma.     

Immunostaining of the estrogen receptor in conjunctival primary acquired melanosis

Conjunctival primary acquired melanosis (PAM) is a frequent precursor of conjunctival melanoma. Since there is indirect evidence that the conjunctiva is an estrogen-responsive tissue, and since it was suspected that estrogen has a role in the etiology of melanoma, we decided to evaluate whether PAM may be responsive to estrogen. Formalin-fixed, paraffin-embedded sections from 13 cases of PAM and 2 cases of conjunctival melanoma were immunostained with an estrogen-receptor (ER)-specific antibody. All lesions and the normal conjunctival tissue adjacent to the lesions were found to be ER negative. It is concluded that PAM and normal conjunctiva are not sensitive directly to estrogen. When considering previously reported data, it is conceivable that the normal conjunctiva, but not PAM, is indirectly affected by estrogen.     

Evaluation of a short-term topical interferon α-2b treatment for histologically proven melanoma and primary acquired melanosis with atypia

Objective: To evaluate the efficiency of series of 6-week treatments with brief intervals (6-week = 1 cycle) of topical Interferon α-2b (IFNα-2b) treatment in primary acquired melanosis (PAM) with atypia and melanoma of the conjunctiva.

Patients and Methods: Five patients with biopsy-proven PAM with atypia and seven patients with melanoma of the conjunctiva, treated with topical IFNα-2b (1 million units/ml, 5 times daily), were included in the study. All patients had colour photographs and the tumour area was measured manually for each patient before and after treatment.

Results: The median age of 12 patients at initiation of treatment was 61.5 years (range 39–75 years). The mean therapy duration was 2.4 cycles (range 1-6 cycle).

Compared to pretreatment lesion dimension, the mean decrease in tumour size were after the first cycle 66% (range 18–98%; p = 0.004; n = 10 patients), after the second cycle 55% (range 10–100%; p = 0.016; n = 7 patients), and after the third cycle 74% (range 23–100%; n = 3 patients). In one patient 6 cycles of topical IFNα-2b were needed. The decrease in size was 22% after the 4^th cycle, 34% after the 5^th cycle, and 98% after the 6^th cycle.

Conclusion: Our clinical experience demonstrates promising results of topical IFNα-2b treatment for PAM with atypia and melanoma of the conjunctiva without any local or systemic side effects. However, future multicenter prospective studies are recommended to confirm the efficiency and safety of topical IFNα-2b treatment.