Regional Treatment Options for Patients With Ocular Melanoma Metastatic to the Liver

Ocular melanoma is the most common primary ocular malignancy and has a significant predilection for metastasis to the liver. More than 40% of patients have hepatic metastases present at initial diagnosis, and the liver becomes involved in up to 95% of individuals who develop metastatic disease. The median survival of patients after diagnosis of liver metastasis ranges from 2 to 7 months. Metastatic disease localized to the liver has proven to be resistant to most available chemotherapy and immunotherapy regimens. Recognition of the grave prognosis associated with liver metastasis from ocular melanoma has led to the evaluation of new regional treatment modalities primarily designed to control tumor progression in the liver, including hepatic arterial chemotherapy, hepatic artery chemoembolization, regional immunotherapy, isolated hepatic perfusion, and percutaneous hepatic perfusion. This article reviews the efficacy, outcomes, and morbidities of the multiple locoregional therapies available today.     

Hepatic Resection for Metastatic Melanoma: Distinct Patterns of Recurrence and Prognosis for Ocular Versus Cutaneous Disease

Background Resection of melanoma metastatic to the liver remains controversial. We evaluated the efficacy of hepatic resection in patients with metastatic ocular and cutaneous melanoma and assessed factors that could affect survival after resection. Methods Forty patients with hepatic melanoma metastasis underwent resection at four major hepatobiliary centers. Clinicopathologic factors were evaluated with regard to recurrence and survival by using χ² and log-rank tests. Results The primary tumor was ocular in 16 patients and cutaneous in 24. The median disease-free interval from the time of primary tumor treatment to hepatic metastasis was the same for both groups (ocular, 62.9 months; cutaneous, 63.1 months; P = .94). Most patients underwent either an extended hepatic resection (37.5%) or hemihepatectomy (22.5%). Twenty-six patients (65%) received perioperative systemic therapy. Thirty (75.0%) of 40 patients developed tumor recurrence. The median time to recurrence after hepatic resection was 8.3 months (ocular, 8.8 months; cutaneous, 4.7 months; P = .3). Patients with primary ocular melanoma were more likely to experience recurrence within the liver (53.3% vs. 17.4%; P = .015), whereas patients with a cutaneous primary tumor more often developed extrahepatic involvement. The 5-year survival rate for patients with a primary ocular melanoma was 20.5%, whereas there were no 5-year survivors for patients with cutaneous melanoma (P = .03). Conclusions Patterns of recurrence and prognosis after resection of hepatic melanoma metastasis differ depending on whether the primary melanoma is ocular or cutaneous. Resection should be performed as part of a multidisciplinary approach, because recurrence is common.     

Testicular Choriocarcinoma Metastatic to the Skin

Pure testicular choriocarcinoma with metastasis to the skin is a very rarely seen phenomenon. Choriocarcinoma has a distinct propensity for early hematogenous spread to distant sites. We present the case of a 42-year-old white male with testicular choriocarcinoma with skin metastasis.     

Surgery for Melanoma Metastatic to the Gastrointestinal Tract

Background: Gastrointestinal (GI) metastasis from melanoma has a dismal prognosis with few long-term survivors. We evaluated the role of operative intervention for melanoma metastases to the GI tract and attempted to identify prognostic factors to improve selection of patients for surgery.Methods: Between 1977 and 1997, 68 of the 7965 patients with melanoma admitted to Memorial Sloan-Kettering Cancer Center underwent surgical exploration for melanoma metastatic to the GI tract. Characteristics of the primary tumor, regional lymph nodes, and metastatic pattern were reviewed. Data concerning the presenting signs and symptoms, laboratory values, operative findings, extent of surgical resection, recurrence pattern, and survival were analyzed.Results: The most common presenting clinical features included anemia (n = 41; 60%) or abdominal pain (n = 40; 59%). The most frequently involved portion of the GI tract was the small bowel (n = 62; 91%), and the most common operative procedure was small bowel resection (n = 54; 79%). Postoperative mortality and morbidity were 2.9% (n = 2) and 8.8% (n = 6), respectively. Presenting symptoms were relieved in 90% of patients (n = 61). Median survival for all 68 patients following operative intervention was 8.2 months, with 18% survival at 5 years. By multivariate analysis, complete resection rendering the patient free of all identifiable disease (n = 19, median survival 14.9 months, 38% survival at 5 years) and a low preoperative serum lactate dehydrogenase (LDH) (n = 28, median survival 13.6 months, 35% survival at 5 years) were identified as independent favorable prognostic factors for survival.Conclusions: Operative intervention for melanoma metastatic to the GI tract is recommended for palliative reasons and can be performed with low morbidity and mortality. It is associated with prolonged survival in patients rendered free of all identifiable disease following surgical resection and in those with a low preoperative serum LDH.Presented at the 52nd Annual Meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Ultrarapid Staining for Cutaneous Melanoma: Study and Protocol

Background Immunohistochemistry has revolutionized the use of frozen sections for the removal of melanoma.
Objective Two studies were performed to address the best and fastest way to stain melanocytes in frozen tissue sections.
Materials and Methods Fifty-six standing cones were taken from sun-damaged white skin and stained with combinations of anti–S-100, anti–HMB-45, anti–Melan-A, and azure B with appropriate controls.
Results Anti–Melan-A was the best immunohistochemical stain. Azure B stains melanin granules metachromatically green and allows differentiation of melanocytes and melanophages. Ultrarapid staining worked as well as rapid staining.
Conclusion Dako's EnVision ultrarapid staining protocol and azure B counterstain represent a dramatic improvement and should be considered the easily obtainable histologic standard when excising cutaneous melanoma     

Surgical Management of Solitary Metastatic Melanoma

Background: Pressure ulcers are a frequent complication of bed rest. The development of an efficient and low cost pressure relieving system for the prevention of bed-sores would be of considerable hospital health and economic interest. Our study was designed to determine the effectiveness in pressure-sore prevention of an interface pressure-decreasing mattress, the Kliniplot® mattress, used in our institution since 1978.

Methods: In a prospective randomised controlled 7-month clinical trial we compared the Kliniplot® mattress with our standard hospital mattress in 1729 patients admitted to medical and surgical departments (neurology, cardiology, oncology-haematology, neurosurgery, thoracic surgery and orthopaedic surgery). Two groups (Klinipot^® mattress and standard hospital mattress) were monitored for the prevention of pressure sores. The patients were evaluated on a daily basis from their admission until the eventual occurrence of a bed-sore. Patients’ characteristics and pressure-sore risk factors were similar at the baseline in both groups. Patients presenting with a pressure sore at the time of admission were excluded.

Results: Forty-two of the 1729 patients (2.4%) who entered the study developed at least one pressure sore. Twenty-one of the 657 patients (3.2%) nursed on the Kliniplot® mattress, and 21 of the 1072 patients (1.9%) on the standard mattress developed bed-sores (p = 0.154). The median time for the occurrence of pressure sores was 31 days (range 687) with the Kliniplot® mattress and 18 days (range 2 to 38) with the standard mattress (p < 0.001). The risk categories for developing bed-sores using the modified Ek’s scale were no different at the baseline between both groups (p = 0.764). The severity of the pressure sores was no different between both groups (p = 0.918).

Conclusions: Our results show that the occurrence of pressure sores is not reduced but is delayed when patients are nursed on a Kliniplot^® pressure-decreasing mattress.     

Metastatic Melanoma in the Gallbladder: Report of a Case

Both primary and secondary gallbladder melanomas are rare and, when a solitary melanoma is found in the gallbladder, it is difficult to determine if it is primary or metastatic disease. We report the case of a young woman found to have a single metastatic gallbladder melanoma. Surgical removal of a solitary metastatic focus remains the treatment of choice for isolated metastasis of a malignant melanoma; however, the effectiveness of complementary chemotherapy and immunotherapy is still being examined. Received: October 15, 2001 / Accepted: July 2, 2002 Reprint requests to: D. Mantas     

Skin Cancer in Asians: Part 2: Melanoma

The Asian population in the United States is expected to increase in the next 50 years. Concurrently, there is an overall rise in the incidence of melanoma. It is therefore crucial to obtain a better understanding of this deadly skin cancer in this minority population, as little information is currently available and prognosis remains poor. Through a review of the literature, this paper explores melanoma in the Asian population, including the most common subtype encountered, prognosis, theories on pathogenesis, and molecular biology.The National Cancer Institute estimates that 39,080 men and 29,640 women will be diagnosed with cutaneous melanoma (CM) in 2009.1 It is further estimated that of those diagnosed with melanoma, 8,650 men and women will die in the United States.1 The US census bureau projects that the Asian population will triple in the next 50 years.2 With an overall rise in melanoma and anticipated increases in the Asian population, clinicians and patients alike must be aware of the potential for skin cancer in this minority population. Currently, there is limited available data on skin cancer in Asians, including melanoma.CM is predominantly an ultraviolet (UV) light-induced skin cancer more commonly associated with light-skinned Caucasians than in individuals with darker skin.³ Traditionally, clinical features associated with CM included Fitzpatrick skin types I to III with lighter color hair and eyes, an increased tendency to burn, history of multiple nevi, and strong family history of CM.⁴ Therefore, it is generally recognized that CM rarely affects individuals of ethnic backgrounds other than Caucasians, including those of Asian, Indian, Hispanic, or African descent. It is believed that greater concentrations of melanin in these darker skin populations provides photoprotective activity against the carcinogenic effects of UV radiation.³ More specifically, increased levels of melanin in darker skin tones are thought to allow less damage to deoxyribonucleic acid (DNA) in the lower epidermis, and more effectively prevents proliferation of UV-damaged cells via apoptosis.³ Consequently, CM in these individuals tends to occur at anatomic locations that are not continually sun-exposed, such as the feet.     

The Density and Distribution of Melanocytes Adjacent to Melanoma and Nonmelanoma Skin Cancers

BACKGROUND: The determination of clear margins during Mohs surgery for melanoma in situ arising on sun-damaged skin is often made difficult by the presence of background atypical melanocytic hyperplasia. OBJECTIVE: To determine the density and distribution patterns of melanocytes adjacent to melanoma and nonmelanoma skin cancers. METHODS: 180 skin specimens obtained during the routine repair of defects resulting from the removal of melanoma and nonmelanoma skin cancers were analyzed using H and E-stained permanent sections to determine the quantity and distribution of epidermal melanocytes. RESULTS: The mean melanocyte density was 7.97 melanocytes per 1 mm of epidermis (SD,+/-6.7). Contiguous melanocytes were found in 30 (16.7%), atypical melanocytes were observed in 8 (4.4%), and follicular extension of melanocytes was observed in 11 (6.1%) of the specimens. These features were significantly associated with higher melanocyte densities (p< .001) and were more commonly observed in specimens from patients with melanoma. CONCLUSIONS: There is a high degree of variability in melanocyte densities seen adjacent to melanoma and nonmelanoma skin cancers. Contiguous melanocytes, atypical melanocytes, and follicular melanocytes can be seen in the sun-damaged skin surrounding both melanoma and nonmelanoma skin cancers, but especially with melanoma. Because some of the features of melanoma in situ can be seen in chronically sun-damaged skin, the Mohs surgeon should be cautious when assessing the margins for melanoma in this setting.     

Prognostic Value of BRAF V600 Mutations in Melanoma Patients After Resection of Metastatic Lymph Nodes

Purpose

BRAF ^V600 mutations are frequent in melanomas, and BRAF^V600-targeted therapy have dramatic, but often transitory, efficacy in stage IV patients. Prognosis of patients with American Joint Committee on Cancer (AJCC) stage III melanoma is heterogeneous. We aimed to determine the overall survival (OS) of stage III patients with a nodal deposit of ??2?mm according to BRAF ^V600 mutations and other previously reported prognostic criteria.

Methods

This retrospective study included 105 consecutive patients with stage III cutaneous melanomas. Most patients underwent a prospective follow-up. BRAF ^V600 mutations were detected by sequencing and pyrosequencing of DNA in samples containing >60?% melanoma cells.

Results

BRAF mutations (p.V600E and p.V600K in 83 and 14?% of cases, respectively) were detected in 40?% of the patients. For patients with and without BRAF mutations, death occurred in 83.3 and 60.3?%, with a median OS of 1.4 and 2.8?years, respectively. Patient age, primary melanoma ulceration, number of invaded lymph nodes, AJCC staging at study entry, and BRAF status were linked to OS in the univariate analysis. The only characteristics associated with OS in the multivariate analysis were number of invaded lymph nodes (P?=?0.005, hazard ratio 2.2, 95?% confidence interval 1.3?C3.9) and BRAF status (P?=?0.005, hazard ratio 1.9, 95?% confidence interval 1.2?C3.1).

Conclusions

BRAF ^V600 status could be used to stage melanoma patients with nodal deposits. Our results may also help to plan adjuvant trials in these patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies.     

Malignant Melanoma of the Skin: Long-term Follow-up and Time to First Recurrence

Background  

Surgical excision can cure most patients with malignant melanoma of the skin. However, the risk of recurrence remains for years. The aim of our study was to identify factors that influence time to recurrence and survival after the first recurrence with a special interest in late recurrences.     

Uterine epithelioid leiomyosarcomas with clear cells: reactivity with HMB-45 and the concept of PEComa

In this study, we investigated HMB-45 expression in epithelioid uterine leiomyosarcomas with clear cell areas. From 12 epithelioid leiomyosarcomas, we selected 5 that had: 1) clear cell areas and 2) spindle cell areas that were at least focally positive for desmin and caldesmon. The patients' ages ranged from 47 to 82 years (mean 64 years). Presenting symptoms were uterine bleeding (three), abdominal pain (one), and a pelvic mass (one). There was no history of tuberous sclerosis or lymphangioleiomyomatosis. One patient had stage II disease, one stage III, and three stage IV. All were treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy. Two received radiotherapy, and three were also treated with chemotherapy. The tumors ranged in size from 4 x 3 x 3 cm to 10 x 7 x 6 cm; all had significant cellular atypia, areas of coagulative necrosis, and between 10 and 90 mitoses per 10 high power fields. Vascular invasion was seen in three cases. The epithelioid component varied from 50% to 90% in each case; and the percentage of clear cells was < 1% in one case, 5% in one case, and 10% to 80% in three cases. Smooth muscle actin and desmin were positive in all cases. Four cases were positive for HMB-45 only in the clear cell areas. The tumor with < 1% of clear cells was negative for HMB-45. All were negative for S-100 and c-kit. Three patients died of disease at 9, 30, and 32 months; one patient is alive with progressive disease at 6 months, and one patient (stage II disease) is alive with no evidence of disease at 8 months. Unequivocal uterine epithelioid leiomyosarcomas may have clear cells positive for HMB-45. These tumors might belong to the group of lesion designated as PEComas; however, it is advisable to designate them as uterine leiomyosarcomas. In uterine smooth muscle tumors, some epithelioid cells most likely undergo clear cell changes and become positive for HMB-45. It would be advisable to perform this stain in all epithelioid smooth muscle tumors of the uterus.     

Long-Term Survival After Complete Resection of Melanoma Metastatic to the Adrenal Gland

Background: Survival of patients with American Joint Committee on Cancer stage IV melanoma is generally poor, although there are occasional long-term survivors who have undergone surgical resection of a limited number of metastases. In the study, we examined the outcome of patients with adrenal gland metastases.Methods: Eighty-three patients with adrenal metastases were identified from our computerized melanoma database of 8250 patients. Univariate and multivariate analyses for overall survival differences were performed by using proportional hazards modeling.Results: Median survival for the 83 patients was 9.3 months (1–67 months). Of the 27 patients who underwent surgical exploration, 18 (66%) were rendered clinically free of disease by adrenalectomy alone (12 cases) or by adrenalectomy and resection of additional disease (6 cases). Nine patients underwent palliative adrenal resection. Median survival was 25.7 months after complete resection compared with 9.2 months after palliative resection (P = .02). Conclusions: Patients with adrenal metastases from melanoma, either isolated or with a limited number of additional metastases, may benefit from surgical resection if all visible disease can be removed. Patients with unresectable extra-adrenal disease achieve no survival benefit from adrenalectomy.Presented at the 51st Annual Cancer Symposium of the Society of Surgical Oncology, San Diego, California, March 26–29, 1998     

Isolated Hepatic Perfusion with High-Dose Melphalan Results in Immediate Alterations in Tumor Gene Expression in Patients with Metastatic Ocular Melanoma

Background  

Patients with ocular melanoma liver metastases have a poor prognosis, treatment options are limited, and median survival is less than 1 year. In this study, we characterized the early molecular changes that occur in tumors immediately after vascular isolation perfusion with melphalan with hyperthermia in patients with hepatic metastases from ocular melanoma.     

Metastatic Melanoma to the Colon,Rectum, and Anus: A 50-Year Experience

Background

Melanoma metastatic to the large bowel (colon, rectum, and anus) is rarely diagnosed, with more than 95% of large bowel metastases identified post-mortem. The incidence, natural history, and survival rates of patients with large bowel melanoma metastases are poorly documented in the literature.

Objective

This study aimed to identify the incidence, clinical characteristics, and survival of patients with large bowel melanoma metastases.

Methods

A review was undertaken of all patients with melanoma treated over a 50-year period (1964–2014) at a tertiary referral center. Cases selected for study were those diagnosed with melanoma metastases in the colon, rectum, and anus. Primary colorectal and anal melanomas were excluded. Data were retrieved relating to patient demographics, clinical features, and survival.

Results

Of 38,279 patients with primary melanoma, 106 patients (0.3%, mean age 51.0 years [standard deviation 16.3], 64 males) developed large bowel metastases. The median interval between diagnosis of primary melanoma and large bowel metastasis was 62.8 months (range 1–476). The most common symptom was rectal bleeding (29.2%), and the large bowel was the sole site of metastasis in 47.2% of patients. Median survival from diagnosis of large bowel metastasis was 31.7 months (range 1–315), and overall survival at 1, 2, and 5 years was 68.1, 45.9, and 26.5%, respectively.

Conclusion

Our study provides insights into melanoma metastatic to the colon, rectum, and anus, which had an incidence of 0.3%. There are potentially long intervals between diagnosis of primary melanoma and large bowel metastasis. The most common symptom was rectal bleeding, although some patients were asymptomatic.