Extramammary Paget's disease resistant to surgery and imiquimod monotherapy but responsive to imiquimod combination topical chemotherapy with 5-fluorouracil and retinoic acid: a case report

Extramammary Paget's disease (EMPD) is an uncommon skin neoplasm that usually affects the elderly population and occurs in the genital, anorectal, or axillary areas. The recommended treatment of EMPD involves surgical excision, including Mohs micrographic surgery; however, surgery is associated with a high rate of recurrence. There have been reports of successful treatment of recurrence with monochemotherapy involving topical imiquimod 5% cream. We report a case of EMPD recurrence after surgery that was resistant to imiquimod monotherapy but that completely resolved after imiquimod was combined with topical 5-fluorouracil (5-FU) and retinoic acid. To our knowledge, this is the first reported case of imiquimod combination therapy with 5-FU and retinoic acid for the treatment of recurrent EMPD.     

Extramammary Paget's disease treated with topical imiquimod 5% cream

Extramammary Paget's disease (EMPD) is a rare cutaneous, intraepithelial adenocarcinoma usually found in the apocrine gland bearing areas. It is traditionally treated with surgery but has a high rate of recurrence. Of late, topical imiquimod 5% cream has come into use as another treatment option. We present two cases of EMPD in Asian skin treated successfully with topical imiquimod 5% cream.     

Topical imiquimod in the treatment of extramammary Paget's disease: A 10 year retrospective analysis in an Asian tertiary centre

Extramammary Paget's disease (EMPD) is a rare intraepithelial adenocarcinoma usually found in apocrine‐rich areas. Although surgery remains standard treatment, topical imiquimod has emerged as a promising drug for the treatment of EMPD in recent years. We present our experience in treating EMPD in Asian skin successfully with topical imiquimod 5% cream, over the past 10 years in our tertiary institution.     

Extramammary Paget disease successfully treated with topical imiquimod 5% and tazarotene

Extramammary Paget disease (EMPD) is an intraepithelial adenocarcinoma usually localized in areas rich in apocrine sweat glands. Surgery remains the treatment of choice for EMPD. However, several nonsurgical treatments have been also described. Around 40 cases of EMPD treated with imiquimod 5% have been published; of these, only six correspond to nonresponses. We describe a recurrent vulvar EMPD with failure to respond to topical imiquimod 5% in monotherapy but a favorable response to its association with tazarotene.     

Treatment of limited extent extramammary Paget's disease with 5 percent imiquimod cream

Extramammary Paget's disease (EMPD) is a rare neoplastic condition of apocrine gland-bearing skin, which may be associated with internal malignancy. Although surgical excision is the generally accepted standard of care for EMPD, treatment with topical imiquimod 5 percent cream has reportedly been efficacious in clearing lesions. We report the case of a 78-year-old woman with biopsy-proven EMPD of the thigh treated successfully with imiquimod application thrice weekly for 16 weeks.     

Extramammary Paget Disease: Minimal Surgical Therapy

Background

Extramammary Paget disease (EMPD) is an uncommon malignant neoplasm affecting apocrine gland-bearing skin which usually occurs in the anogenital area of patients older than 50 years. Although Mohs micrographic surgery (MMS) is recommended for the treatment of EMPD, wide local excision has also been performed by many other surgeons including dermatosurgeons. However, the extent of an adequate resection margin is still under debate.

Objective

The efficacy of minimal surgical therapy consisting of a wide excision combined with preoperative multiple scouting biopsies and postoperative topical imiquimod was investigated for the treatment of EMPD in Korean patients.

Methods

Between 2006 and 2012, 10 patients with primary EMPD were treated with wide surgical excision, with a surgical margin of less than 2.5 cm. Multiple preoperative scouting biopsies and postoperative topical imiquimod were also performed to delineate the lesional boundaries and to reduce the recurrence rate.

Results

During the 6-year follow-up period, complications and recurrences were not observed.

Conclusion

Minimal surgical therapy may be an effective alternative when MMS is unavailable.     

Imiquimod 5% cream as a therapeutic option for extramammary Paget's disease

A wide local excision is the standard treatment for extramammary Paget's disease (EMPD), though this treatment often leads to permanent anogenital mutilation and functional impairment. The purpose of our study is to evaluate the efficacy and safety of the topical application of imiquimod 5% cream for non‐invasive EMPD. We examined nine patients with EMPD. Eight of the nine patients were treated with imiquimod 5% cream three times per week for 16 weeks; one case was treated for 6 weeks. The response rate was 100% including five complete remissions. Local irritation was observed in three patients, which was controlled by a provisional withdrawal of the treatment. These results suggest that imiquimod 5% cream may be considered an alternative therapeutic option for the treatment of non‐invasive EMPD.     

Photodynamic therapy for the treatment of extramammary Paget's disease

BACKGROUND: Surgical and ablative treatment modalities for extramammary Paget's disease (EMPD) have high recurrence rates and can be associated with significant morbidity. OBJECTIVES: To evaluate photodynamic therapy (PDT) for the treatment of EMPD. METHODS: We conducted a retrospective review of notes and histology of five men with anogenital, groin and axillary EMPD treated with PDT at Roswell Park Cancer Institute between 20 April 1995 and 1 February 2001. RESULTS: Sixteen EMPD lesions were treated with topical aminolaevulinic acid (ALA)-PDT. Eleven of these lesions had failed previous Mohs micrographic surgery, excision or laser ablation. When evaluated 6 months after one treatment with ALA-PDT, eight of 16 (50%) sites achieved a complete clinical response (CR); six of eight CRs were in lesions that had failed prior conventional therapies. Three of the eight CRs (37.5%) recurred at 9, 10 and 10 months. One patient who was partially responsive to topical ALA-PDT subsequently received systemic Photofrin(R)-PDT, with a complete clinical and histological response at 1 year. Functional and cosmetic outcome was excellent in all patients. CONCLUSIONS: PDT is an effective treatment for EMPD. Recurrence rates are high with topical ALA-PDT, but comparable with standard therapies. Topical ALA-PDT causes little scarring and is preferred for superficial disease and mucosal surfaces. Systemic Photofrin(R)-PDT may be better suited for bulky disease. While further studies are indicated, PDT is well tolerated and appears to be a useful therapy for EMPD.     

Successful treatment of three cases of primary extramammary Paget’s disease of the vulva with Imiquimod – proposal of a therapeutic schedule

Background/aim Extramammary Paget‘s disease (EMPD) is an intraepidermal adenocarcinoma of apocrine gland‐bearing skin. Although surgery remains the mainstay of treatment, loss of tissue function and high recurrence rates have been reported. Recently, topical Imiquimod has been shown as a safe and effective treatment option for extramammary Paget‘s disease. Methods Three patients diagnosed of EMPD of the vulva were treated with a daily application of 5% Imiquimod cream for three weeks, followed by an every other day application for an additional three weeks. Results Complete clinical and histological remission of the disease was achieved in the three patients. Mild irritation and tenderness were observed as the only side effects. Conclusion Based on our results, we consider that Imiquimod cream is a safe and effective therapeutic option for the treatment of vulvar EMPD. These promising results warrant further studies to determine the real efficacy and safety of Imiquimod 5% cream for the treatment of this uncommon disease.     

Imiquimod 5% cream for the treatment of nasal lesion of metastatic renal cell carcinoma

Many reports have shown the efficacy of topical imiquimod in patients with skin carcinoma. This effect is based on the activity of imiquimod as an immune-response modifier. The present authors hypothesized that this agent could also be used to treat skin metastatic lesion from renal cell carcinoma. The present authors report the case of a 54-year-old man who presented with a metastasis renal cell carcinoma lesion on his nose. He had a history of right nephrectomy performed 4 years previously. The present authors started him on topical treatment with imiquimod 5% cream three times a week for his nose lesion. A reduction of the lesion was observed after 2 months, and during the following 12 months no sign of recurrence was observed.     

Mohs显微手术治疗乳房外Paget病42例

目的:评价Mohs治疗乳房外Paget病的疗效。方法:42例乳房外Paget病患者沿皮损周围2 cm行Mohs手术切除,确认边缘结果阴性之后行皮瓣或植皮闭合。术后31例患者使用光动力,每周1次,共4次。11例外用咪喹莫特乳膏,每日1次,共半年,随访8~36个月。结果:6例患者复发,复发率14.3%,其中4例为术后光动力治疗患者,2例为术后外用咪喹莫特乳膏。结论:EMPD进行Mohs显微描记手术结合光动力治疗或外用咪喹莫特乳膏有效。     

Successful treatment of perianal warts in a child with 5% imiquimod cream

Treatment of anogenital warts in children is difficult. Commonly used therapeutic regimes can be painful, variably effective and recurrence rates are high. Imiquimod is a recently developed imidazoquinolin heterocyclic amine that is an immune response modifier. Topical imiquimod has been used successfully to treat anogenital warts in adults. This case documents the effective use of topical imiquimod in the treatment of perianal warts in children.     

Cryosurgery during topical imiquimod: a successful combination modality for lentigo maligna

Background Either cryosurgery or topical imiquimod have been used to treat patients with lentigo maligna in cases where surgery is not feasible. Methods We report a patient with lentigo maligna, who was treated with the combination of topical imiquimod and cryosurgery, and review the rationale, which led us to design the present combined cryo‐immunological treatment modality. Results Sustained clearance of lentigo maligna to date (26 months after treatment). The successful treatment of this patient was based on the following rationale: A cryosurgery session during continuing imiquimod application may: (i) reinforce apoptosis of tumor cells; (ii) strengthen antiangiogenesis in the treated tumor; and (iii) build‐up a potent tumor‐destructive immune response by a cascade of events starting with imiquimod‐promoted attraction of immature dendritic antigen‐presenting cells (DCs) into the tumor. DCs further mature within the tumor‐antigen‐rich environment of subsequently cryo‐destructed tumor and upon imiquimod‐driven migration into the peripheral lymph nodes can stimulate a specific antineoplastic cell‐mediated immunity. Finally, continuing imiquimod application after cryosurgery may increase recruitment of activated effector cells into the tumor tissue leading to its destruction. Conclusion Cryosurgery during continued topical imiquimod seems to be a promising treatment for lentigo maligna.     

5-Aminolevulinic acid-based photodynamic therapy for the treatment of two patients with extramammary Paget's disease

Photodynamic therapy (PDT), which employs a combination of a tumor-localizing photosensitizer and visible light, has been used in the treatment of extramammary Paget's disease (EMPD). Two patients with EMPD were treated with PDT using 5-aminolevulinic acid (ALA). Histologically, in both cases, Paget's cells were present within the epidermis. Case 1 was a 92-year-old male who underwent total extirpation for treatment of EMPD. Two topical ALA-PDT treatments were applied to parts of the lesions at a total dose of 200J/cm2. Case 2 was a 73-year-old female, whose lesions in the right labia majora were treated with 3 topical ALA-PDT sessions at a total dose of 300 J/cm2. Clinical findings after the irradiation showed improvement in both patients, and elimination of tumor cells in the epidermis was confirmed histologically. Case 1 had no recurrence in the irradiation field at three months after PDT. Case 2 had a recurrence only in the periphery parts of the lesions at two months after PDT, but the periphery lesions remitted with two more PDT treatments. Topical ALA-PDT is an effective treatment for EMPD with tumor cells within the epidermis. It is noninvasive and achieves a cosmetically excellent outcome, especially in elderly patients and those in poor general condition.     

Squamous cell carcinoma in situ of the penis successfully treated with imiquimod 5% cream

BACKGROUND: Multiple treatments for squamous cell carcinoma in situ (SCCIS) of the penis have been used with variable success and morbidity. Surgery and destructive treatment modalities have significant risk of scarring, deformity, and impaired function. OBJECTIVE: The purpose of this study was to determine whether topical imiquimod 5% cream is a potentially effective treatment for SCCIS of the penis and to qualify treatment associated morbidity. METHODS: The case of a patient with extensive penile SCCIS is reported. The patient was treated with topical imiquimod 5%, administered daily until blistering occurred (2 cycles). Biopsy specimens were obtained to confirm tumor clearance. RESULTS: One month after therapy was completed, no clinical or histologic evidence of residual tumor was found. Adverse effects of imiquimod included localized tenderness and erythema. No evidence of scarring, deformity, loss of function, or tumor recurrence was noted 18 months after treatment. CONCLUSION: Imiquimod 5% cream may represent an alternative treatment option for SCCIS of the penis.     

Treatment options in melanoma in situ: topical and radiation therapy,excision and Mohs surgery

Background The treatment of melanoma in situ (MIS), particularly the lentigo maligna (LM) subtype, has been a controversial subject in the literature for over a decade. Surgical excision with 5 mm margins is the standard of care in the USA, while several variations of Mohs surgery are frequently used to treat clinically ill‐defined lesions. Radiation is much less frequently used. Topical imiquimod has also been more recently proposed, in small case reports in the literature, as a therapy for MIS. However, controversies exist with all approaches. Objective To review the current literature regarding topical imiquimod, radiation therapy, surgical excision, and the various forms of Mohs surgery for MIS, focusing on the LM subtype. Methods A literature search was performed in the PubMed database using the following terms: “melanoma in situ,”“lentigo maligna,”“excisional surgery,”“Mohs micrographic surgery,”“radiation therapy,” and “imiquimod.” Articles relevant to the treatment of MIS were reviewed and reported herein. Results Studies of imiquimod therapy for MIS are hampered by small study numbers and short follow‐up periods. The few, better‐designed studies reveal relatively low cure rates. In addition, literature review reveals that a significant percentage of cases of MIS that are initially diagnosed as in situ disease by biopsy subsequently prove to have an invasive component upon complete excision. This finding suggests that topical therapy of any kind may be problematic. Studies of radiation therapy for MIS have relatively small numbers of patients and short follow‐up. Multiple studies of excisional surgery have shown that 5 mm margins are often insufficient to clear the LM subtype of MIS due to unseen subclinical extension, accounting for this treatment’s reported 8–20% recurrence rate. Finally, a number of variants of traditional frozen section Mohs surgery have been utilized to try and achieve complete peripheral margin assessment of clinically ill‐defined LM lesions. All studies are retrospective, and most are single‐institution and frequently single‐operator, limiting the meaningfulness of their results. Nevertheless, they involve moderate numbers of patients, and many have at least a five year follow‐up. Collectively, they suggest recurrence rates in the range of 0.5–3.0%. Conclusion Topical imiquimod therapy appears to provide relatively low cure rates for MIS, and because some of these lesions contain an unrecognized invasive component, should be used with extreme caution to treat this disease. Radiation therapy may be a useful second‐line therapy if surgery is contraindicated. Excisional surgery is an appropriate therapy for clinically well‐defined MIS; however, margins larger than 5 mm may be required when treating larger or indistinct lesions. Finally, for clinically ill‐defined LM arising on sun‐damaged skin, especially in regions of aesthetic concern, some form of complete peripheral margin assessment – one of the various forms of Mohs surgery – may provide the highest cure rate and create the smallest surgical defect.     

Current modalities and new advances in the treatment of basal cell carcinoma

Basal cell carcinoma (BCC) is one of the most common cancers. Surgical extirpation is currently the standard of care for BCC, which is associated with several advantages and disadvantages. Procedures such as surgical excision used to treat superficial BCC (sBCC) and nodular BCC (nBCC) may have high 5-year recurrence rates if tumors are not completely excised. Curettage with electrodesiccation is a common method for treating primary BCC. However, multiple cycles are recommended and the procedure can have unsatisfactory cosmetic results (e.g. scarring and hypopigmentation). Mohs micrographic surgery has a low rate of disease recurrence but is a specialized procedure usually limited to specific indications (e.g. high-risk tumors). Cryosurgery and photodynamic therapy require multiple cycles and are associated with variable cosmetic outcomes and recurrence rates. As with any procedure, potential risks and patient quality-of-life issues need to be considered. In addition, substantial patient and healthcare provider inconvenience limit the practical utility of some modalities. Pharmacologic interventions provide another treatment option as adjunctive or monotherapy. Investigations of imiquimod, a novel immune response modifier, have indicated that this topical, noninvasive agent is safe and well tolerated and may be efficacious in the treatment of BCC. This review will highlight the role of standard treatment modalities and introduce new advances in the treatment of BCC.     

Progress of multiple cutaneous and subcutaneous melanoma metastases of the face during imiquimod treatment

A 68‐year‐old man developed a local recurrence with multiple cutaneous and subcutaneous nodules three months after excision of a primary malignant melanoma of the temple. Despite extensive surgery and adjuvant irradiation, another local recurrence occurred. Following further local progression during dacarbazine chemotherapy, topical treatment with imiquimod was begun and the chemotherapy was changed to fotemustine. During this treatment further local progression occurred and two months later regional lymph node and distant metastasis were detected. The patient died from his tumor disease eighteen months after the first diagnosis of malignant melanoma.     

周围组织的 Mohs 显微描记外科手术治疗乳房外 Paget 病

目的：探讨周围组织的 Mohs 显微描记外科手术治疗乳房外 Paget 病（EMPD）的有效性。方法对28例 EMPD 患者术前肿瘤侵犯的深度和范围进行判断,术前1 d 外敷20%盐酸氨酮戊酸,伍德灯下观察并标记手术切缘。切取荧光定位后的边缘皮肤组织,按 Mohs 显微描记外科技术方法仅对周围组织进行冰冻切片检查,同时进行肿瘤切除。术后3～6个月随访1次,观察局部复发和转移情况。结果28例患者中,男25例,女3例。6例患者需要3次冰冻切片,12例患者要2次冰冻切片,平均1.86次。随访5～72个月,局部复发者3例,1例尿毒症患者随访2年因肝转移死亡。结论周围组织的 Mohs 显微描记外科手术是一省时和有效的治疗EMPD 的方法。     

Topical Imiquimod for the Treatment of Childhood Cutaneous Langerhans Cell Histiocytosis

Although topical steroids are considered first‐line treatment for cutaneous Langerhans cell histiocytosis (LCH), the appropriate therapy for refractory cases remains controversial. We report a 16‐month‐old girl with isolated cutaneous LCH refractory to treatment with topical corticosteroids and topical tacrolimus. Treatment was initiated with 5% topical imiquimod cream and the rash completely resolved after 5 months of therapy. There was no disease recurrence after more than 2 years of follow‐up. We present this case to highlight imiquimod as a novel therapeutic agent for the management of isolated cutaneous LCH in children.