History Of Cutaneous Melanoma Research Articles

ATLAS: A positive, high-yield review of patient symptoms most significantly associated with melanoma recurrence

BackgroundNo standardized, evidence-based surveillance practices exist to guide and optimize recurrence detection in patients with cutaneous melanoma. ObjectiveTo determine the most high-yield positive review of systems for signaling recurrence in patients with cutaneous melanoma. MethodsThis retrospective cohort study assessed patients with a history of cutaneous melanoma and compared demographic and clinical characteristics, including a comprehensive review of systems, amongst those who developed recurrence and those who did not. ResultsA high-yield positive review of systems associated with cutaneous melanoma recurrence can be remembered using the mnemonic ‘ATLAS’: Appetite change, Tiredness, Lymph node enlargement, Abdominal pain, and Shortness of breath LimitationsRetrospective design, limited sample size, and variability in follow up time between recurrent and non-recurrent cohorts. ConclusionAny treating physician using this model may have a greater opportunity to detect recurrent cutaneous melanoma and improve outcomes while limiting cost and morbidity.

METASTATIC MELANOMA TO THE LUNG CURED WITH LOBECTOMY: A CASE REPORT

METASTATIC MELANOMA TO THE LUNG CURED WITH LOBECTOMY: A CASE REPORT

Genetic Relationship Between Endometriosis and Melanoma.

Epidemiological studies have observed that risk of endometriosis is associated with history of cutaneous melanoma and vice versa. Evidence for shared biological mechanisms between the two traits is limited. The aim of this study was to investigate the genetic correlation and causal relationship between endometriosis and melanoma. Summary statistics from genome-wide association meta-analyses (GWAS) for endometriosis and melanoma were used to estimate the genetic correlation between the traits and Mendelian randomization was used to test for a causal association. When using summary statistics from separate female and male melanoma cohorts we identified a significant positive genetic correlation between melanoma in females and endometriosis (rg = 0.144, se = 0.065, p = 0.025). However, we find no evidence of a correlation between endometriosis and melanoma in males or a combined melanoma dataset. Endometriosis was not genetically correlated with skin color, red hair, childhood sunburn occasions, ease of skin tanning, or nevus count suggesting that the correlation between endometriosis and melanoma in females is unlikely to be influenced by pigmentary traits. Mendelian Randomization analyses also provided evidence for a relationship between the genetic risk of melanoma in females and endometriosis. Colocalization analysis identified 27 genomic loci jointly associated with the two diseases regions that contain different causal variants influencing each trait independently. This study provides evidence of a small genetic correlation and relationship between the genetic risk of melanoma in females and endometriosis. Genetic risk does not equate to disease occurrence and differences in the pathogenesis and age of onset of both diseases means it is unlikely that occurrence of melanoma causes endometriosis. This study instead provides evidence that having an increased genetic risk for melanoma in females is related to increased risk of endometriosis. Larger GWAS studies with increased power will be required to further investigate these associations.

1942 A Rare Source of Gastrointestinal Bleeding Discovered With Capsule Endoscopy

INTRODUCTION: Melanoma accounts for 5% of all skin cancers, with lentigo maligna melanoma (LMM) accounting for 10–15% of melanomas. The LMM variety harbors a risk of invasive progression up to 20%. Studies have shown that the small bowel is a preferred site for melanoma metastasis due to its high vascularity, and approximately 60% of patients diagnosed with melanoma skin cancer will have gastrointestinal (GI) metastasis. The usual time for primary melanoma to GI metastasis is 60–90 months. Metastatic melanoma is a rare cause of GI bleeding but should be considered in all patients with history of cutaneous melanoma. This case report presents a man with history of LMM who presented with melena and capsule endoscopy identified small bowel metastasis of the primary cutaneous melanoma. CASE DESCRIPTION/METHODS: A 78-year-old man with medical history of cutaneous melanoma and Mohs surgical resection 2 years prior presented to the emergency department for melena over a 2-week duration. One year before this admission the patient presented with similar complaints and esophagogastroduodenoscopy (EGD) with colonoscopy did not yield a bleeding source. At admission he was hemodynamically stable with a hemoglobin of 9.7. Hemoccult testing in the emergency department was negative, but the patient was admitted for monitoring. Gastroenterology was consulted and because the patient had a stable hemoglobin during his stay without hemodynamic compromise, and in-light of recent negative EGD and colonoscopy, the decision was made to follow-up outpatient with capsule endoscopy (CE). On review of CE footage, the patient was found to have an ulcerated mass with active bleeding in the small bowel. Biopsy confirmed the mass was metastatic melanoma. The patient was referred to oncology who found multiple boney and liver metastases and started him on Nivolumab and Zometa. DISCUSSION: Metastatic melanoma spreads to the small bowel in 60% of cases. As in this case, metastatic melanoma to the small bowel can cause an occult GI bleed, or even massive bleeding and hematemesis, with some cases of intussusception also reported. Whatever the presentation, one should have a high index of suspicion of metastasis in patients with a history of cutaneous melanoma and new GI bleeding. Negative EGD and colonoscopy should prompt an investigation with CE to rule out metastatic lesions.

Histomorphologic spectrum of germline-related and sporadic BAP1-inactivated melanocytic tumors

BRCA1-associated protein 1 (BAP1)-inactivatedmelanocytic tumors (BIMTs) are often the earliest sign of the BAP1 tumor predisposition syndrome. Identification of BIMTs and selection of patients for germline testing affect the lives of patients with germline BAP1 mutations. To describe the spectrum of histomorphologic findings in BAP1-inactivated melanocytic lesions to improve their recognition. We determined the frequency of sporadic versus germline cases in our cohort, assessing whether any features were statistically linked to germline status. Histomorphologic features of BAP1-inactivated melanocytic lesions were analyzed by comparing cases with germline mutations with those with unknown or negative status. Available clinical follow-up data were reported. The histomorphologic spectrum of BAP1-inactivated melanocytic lesions is broad; it includes cases with spitzoid cytomorphology (69%), smaller epithelioid cells without spitzoid features (31%), and rhabdoid cytologic features (58%). BIMTs from patients with germline mutations were statistically more likely to have an extensive junctional component of BAP1-inactivated melanocytes (P=.0177). All 11 patients with suspected or confirmed germline mutations had a history of cutaneous melanoma or multiple BIMTs. The unknown germline status of 77 patients. Approximately 12% of patients with BIMTs have germline mutations. Extensive junctional involvement in a BIMT and a personal history of melanoma or previous BIMT may be additional indications for germline testing.

Sonographic differentiation between lymphatic and metastatic diseases in cervical lymphadenopathy.

The spectrum of differential diagnosis in cervical lymphadenopathy is extremely broad. In lymphoma and inflammatory diseases, surgical approaches are restricted to diagnostic lymph extirpation, whereas metastatic outgrowth into regional lymph nodes usually requires neck dissection. Lymph node surgery has to manage the balancing act between sufficient radicality and preservation of functional structures. The current study, therefore, aimed to identify parameters to differentiate between lymph nodes of lymphatic and metastatic origin. Single-center, retrospective cohort study. Clinical and sonographic parameters from all patients who underwent diagnostic cervical lymphadenectomy from 2010 to 2015 (N = 262) were included in this retrospective analysis. Parameters with significant differences between the two subgroups were utilized to create a clinical algorithm to distinguish between cervical lymphadenopathy of lymphatic and metastatic genesis. Statistically significant differences between the two subgroups could be shown for clinical (gender, age, nicotine/alcohol abuse, B symptoms, history of cutaneous melanoma, or lymphoma) and ultrasonographic parameters (string-of-beads confirmation, bilaterality, homogenous echostructure, localization in level I, long-to-short axis ratio, and hilar vascularity). The proposed algorithm yielded a sensitivity of 92.4% for metastatic disease. The implemented algorithm based on ultrasonographic and clinical criteria contributes to one-step surgical approaches that guarantee a sufficient radicality with a minimum of functional loss. 4. Laryngoscope, 128:859-863, 2018.

Methotrexate treatment in patients with a history of cutaneous melanoma and the risk of a consecutive primary melanoma: A national retrospective registry-based cohort study

Methotrexate treatment in patients with a history of cutaneous melanoma and the risk of a consecutive primary melanoma: A national retrospective registry-based cohort study

Risk of other Cancers in Families with Melanoma: Novel Familial Links

A family history of cutaneous melanoma (‘melanoma’) is a well-established risk factor for melanoma. However, less is known about the possible familial associations of melanoma with other discordant cancers. A risk for discordant cancer may provide useful information about shared genetic and environmental risk factors and it may be relevant background data in clinical genetic counseling. Using the Swedish Family-Cancer Database, we assessed the relative risk (RR) for any cancer in families with increasing numbers of first-degree relatives diagnosed with melanoma, including multiple melanoma, and in reverse order RR for melanoma in families of multiple discordant cancers. Close to 9% of melanoma was familial; among these 92% were in 2-case families and 8% in families with 3 cases or more. Cancers that were associated with melanoma, in at least two independent analyses, included breast, prostate, colorectal, skin and nervous system cancers. Other associations included cancer of unknown primary, acute myeloid leukemia/myelofibrosis and Waldenström macroglobulinemia/myeloma. Significant results, which appear biologically plausible, were also obtained for rare nasal melanoma and mesothelioma. Although small samples sizes and multiple comparisons were of concern, many of the above associations were internally consistent and provide new diverse leads for discordant familial association of melanoma.

Breast Metastasis from Cutaneous Malignant Melanoma Mimicking a Breast Cancer

Introduction Breast metastases are very uncommon, either from solid tumors or malignant melanoma. Case report We present the case of a 42-year-old woman with a history of cutaneous melanoma of the shoulder excised 21 years ago. She presented with a palpable lump in the upper outer quadrant of the right breast. Ultrasound demonstrated a solid mass within a cystic lesion. A core biopsy was taken and first histology reported a poorly differentiated primary breast cancer suspected to be triple negative. MRI detected a satellite lesion in the same breast, a focus of suspected enhancement in the other breast, and the extramammary finding of an enhancing pulmonary lesion. Staging computed tomography detected widespread metastases to the lungs, brain, subcutaneous left shoulder, liver, pancreas, and hepatorenal recess. A core biopsy was taken from the left breast lesion and the previous slides were reviewed; histopathology and immunohistochemistry were in keeping with metastasis from melanoma. Conclusions The possibility of a metastatic lesion to the breast should be taken into account in any patient presenting with a breast lump and a previous history of melanoma. Breast involvement cannot be considered an isolated finding, as it might be the first manifestation of widespread disease.

A Rare Case of Gastrointestinal Bleeding Due to Primary Intestinal Melanoma

Introduction: We present a rare case of primary small intestine melanoma. Case Report: A 69-year-old male with a history of colon polyps presents with dark stool and fatigue. His hemoglobin dropped from 16 to 11. EGD showed possible Barrett’s esophagus. Biopsy was negative for metaplasia. He had a nodule of the second portion of the duodenum. Biopsy showed normal mucosa. Colonoscopy showed hemorrhoids, diverticulosis, and normal terminal ileum. A 3-mm tubular adenoma was removed from the colon. Small bowel (SB) capsule showed a moderate-sized semi-circumferential mass in the jejunum with areas of ulceration and bleeding. A CT abdomen showed small bowel mass in the distal jejunum. Adjacent enlarged lymph nodes (LN) are suspicious for metastatic disease. The patient underwent exploratory laparotomy and partial SB resection. Pathology reveals malignant melanoma. LN was negative for metastasis. Skin evaluation by dermatology did not find any lesions that were concerning for dysplastic nevi. Ophthalmology evaluation was normal. MRI of the brain revealed no metastatic process. PET-CT revealed intense hypermetabolism in the small bowel at the area of the surgical site without any evidence of metastatic disease. He followed up with oncology and his repeat PET scan and capsule endoscopy remained negative for recurrence of cancer. Discussion: Intestinal melanomas can be primary tumors or metastases of cutaneous, ocular, or anal melanomas. Primary intestinal melanoma is extremely rare. Most cases of SB melanoma are metastases from cutaneous melanoma. Metastases to the gastrointestinal tract are found at autopsy in 60% of patients who die with malignant melanoma. The clinical picture of SB melanoma is similar to the clinical presentation of other tumors involving the SB. Thus, patients with a history of cutaneous melanoma who have intermittent abdominal pain or anemia should be investigated to rule out intestinal metastases. Diagnosis can be made by ultrasound, barium studies, endoscopy, CT, or PET. A combination of imaging techniques is recommended to improve the sensitivity and specificity of radiological imaging. No standard therapy exists for the treatment of intestinal melanoma, although surgical removal is the treatment of choice in all patients with resectable melanoma. Accurate preoperative diagnosis and assessment of the extent of intestinal metastases is essential when selecting patients for surgery. Systemic chemotherapy regimens show no benefit to overall survival. The prognosis is poor, with an overall median survival of 6-9 months and a 5-year survival rate of less than 10%. Conclusion: Primary intestinal melanoma is very rare condition with poor prognosis. Early detection and surgical resection are vital to disease survival.

Bilateral Internal Auditory Canal Melanoma

Bilateral Internal Auditory Canal Melanoma

Lack of GNAQ germline mutations in uveal melanoma patients with high risk for hereditary cancer predisposition

A high frequency of somatic mutation in GNAQ has been reported in uveal melanoma (UM). GNAQ is located in the chromosomal band 9q21, the same chromosomal band that harbors a putative candidate gene for hereditary UM. We investigated the frequency of germline sequence alterations in the GNAQ gene in UM patients with increased predisposition to hereditary cancer. A total of 44 high risk UM patients were studied including three patients with a family history of UM, 15 patients with a family history of cutaneous melanoma (CM), three patients with early age at onset of their UM (<30years) and 23 patients with strong family history of cancer and/or personal history of multiple primary tumors. Mutational screening of the seven exons of GNAQ and nearby intronic sequence was carried out by direct sequencing. We identified two deep intronic variants but no potential pathogenic mutations in GNAQ. Our results exclude GNAQ as a candidate gene in UM patients with a high risk for hereditary cancer predisposition.

Melanoma adrenal metastasis: report of 3 cases and literature review

To investigate the clinical diagnosis, treatment and prognosis of melanoma adrenal metastasis. A total of 48 cases of malignant melanoma from 1985 to 2007 were reviewed. And three cases of melanoma adrenal metastasis were analyzed. There were 2 males and 1 female with an age of 57, 70 and 83 years old respectively. Two cases had a history of cutaneous melanoma and another one suffered previously from anal melanoma. The disease-free interval to adrenal metastasis were 25, 37, 33 months respectively. Two presented with flank or abdominal discomfort and another one had adrenal metastasis on routine examination. The maximal diameters of metastasis were 5, 8 and 12 cm respectively. The CT value of adrenal metastasis had a range of 9 - 45 Hu in plain scan. And the maximal post-contrast value was 107.5 Hu. One patient with concurrent lymph node metastasis received non-operative therapy with interleukin-2. The other two cases underwent complete resection of melanoma metastasis. One received adrenalectomy via retroperitoneal laparoscopic approach while another patient with tumor thrombus in inferior vena cava underwent right adrenalectomy and extraction of tumor thrombus out of inferior vena cava in traditional open surgery. When contralateral adrenal metastasis of melanoma was found 6 months later, left adrenalectomy laparoscopically was performed. The patient who was managed non-operatively died of cachexia 6 months later. Two operated patients did not accept adjuvant therapy. One had multiple metastasis in 16 months and died at 21 months. Another was alive without recurrence or new metastasis at 30 months. Melanoma metastasis to adrenal gland is rare and it generally has a poor prognosis. Patients with adrenal metastases from melanoma, either isolated or with a limited number of additional metastases, may achieve a survival benefit from surgical resection if all visible lesions are removed.

Case 1-2009

A 57-year-old man was transferred to this hospital because of progressive cognitive decline. Before admission, he had a generalized seizure, after which he was confused, incoherent, and intermittently agitated; he was admitted to another hospital and transferred 5 days later. His wife reported that he had had episodes of confusion for the past 5 years and worsening memory loss and performance problems for the preceding 2 months. He had a history of cutaneous melanoma, alcohol and drug abuse, and occupational exposure to organic solvents. Magnetic resonance imaging of the brain revealed diffuse signal abnormalities in the white matter. A diagnostic procedure was performed.

Comparison between familial and sporadic cutaneous melanoma in Valencia, Spain

Some clinical, pathological and genetic features have been associated to familial melanoma, particularly multiple melanoma and earlier age at diagnosis. To compare the clinical, epidemiological and pathological differences between familial and sporadic melanoma patients in Valencia, Spain, a series of 959 patients with cutaneous melanoma were selected at a single institution. For this study the following variables were selected: age, sex, melanoma site and presence of solar lentigines on the melanoma surrounding skin, histological subtype, tumor thickness, stage, family and personal history of cutaneous melanoma and of other neoplasias, personal history of non-melanoma skin cancer, past personal history of severe sunburns, cutaneous phenotype (phototype, hair and eyes colors number of common nevus, number of atypical nevi, presence of solar lentigines). Forty-one (4.28%) familial and 918 sporadic melanoma were identified. Among the multiple variables studied, a younger age at diagnosis (median age of 42 vs 53 years), higher frequency of the presence of at least one clinically atypical nevus (36.1% vs 17.7%), multiple melanomas (12.2% vs 3.4%) and red/blonde hair (33.3% vs 18.9%), and a lower rate of cases with solar lentigines in melanoma site (33.3% vs 56.3%) were found for familial cases. Except for hair color and age, the other variables remained statistically significant after the multivariate study. Interestingly, no acral melanomas were found among the familial cases. In summary, phenotypic risk factors for familial melanoma are a tendency to develop multiple melanomas, to have clinically atypical nevi and to present less actinic damage at the melanoma site. All these results enhance the relevancy of genetic susceptibility associated to the ability to produce atypical nevi and partly to a higher sensitivity to the sun.

Primary Melanocytic Tumor of the Cerebellopontine Angle Mimicking a Vestibular Schwannoma.

OBJECTIVE: The majority of tumors of the cerebellopontine angle (CPA) are benign. We report the case of a primary malignant melanoma of the cerebellopontine angle that mimicked vestibular schwannoma (acoustic neuroma). We discuss the differential diagnosis and prognosis of melanotic lesions at this location. CLINICAL PRESENTATION: A 49-year-old man presented with a 7-year history of unilateral deafness and a several month history of imbalance, intractable nausea and vomiting, as well as weight loss. A neurological work-up revealed a large tumor in the left CPA radiographically diagnosed as a vestibular schwannoma. INTERVENTION: A translabyrinthine approach revealed a pigmented, vascular neoplasm encasing vessels and cranial nerves of the left CPA. The tumor was subtotally resected, and a histopathological diagnosis of melanoma was made. The patient had no history of cutaneous melanoma, and no other site of disease was ever discovered. CONCLUSION: This case most likely represents primary melanoma of the central nervous system that mimicked a vestibular schwannoma. The differential diagnosis of melanotic lesions of the CPA is discussed as are the prognostic implications of each diagnosis.

Primary Melanocytic Tumor of the Cerebellopontine Angle Mimickinga Vestibular Schwannoma

The majority of tumors of the cerebellopontine angle (CPA) are benign. We report the case of a primary malignant melanoma of the CPA that mimicked a vestibular schwannoma (acoustic neuroma). We discuss the differential diagnosis and prognosis of melanotic lesions at this location. A 49-year-old man presented with a 7-year history of unilateral deafness and a several month history of imbalance, intractable nausea and vomiting, as well as weight loss. A neurological work-up revealed a large tumor in the left CPA radiographically diagnosed as a vestibular schwannoma. A translabyrinthine approach revealed a pigmented, vascular neoplasm encasing vessels and cranial nerves of the left CPA. The tumor was subtotally resected, and a histopathological diagnosis of melanoma was made. The patient had no history of cutaneous melanoma and no other site of disease was ever discovered. This case most likely represents primary melanoma of the central nervous system that mimicked a vestibular schwannoma. The differential diagnosis of melanotic lesions of the CPA is discussed as are the prognostic implications of each diagnosis.

Clinical and immunocytochemical findings in a case of melanoma-associated retinopathy

Objective To describe an unusual case of melanoma-associated retinopathy (MAR). Design Retrospective, observational case report and experimental study. Participants A 61-year-old man with a history of cutaneous melanoma, acquired bilateral central scotomas, and night blindness. Intervention Serial full-field electroretinography (ERG) and Goldmann perimetry were performed. Serum was screened for cancer-associated retinopathy (CAR) antibodies by Western blotting. Sections of human and rat retina were examined by immunofluorescence microscopy to determine whether retinal cells were reactive with this patient’s serum. A metastatic workup was performed. Main outcome measures Electroretinography, Goldmann visual field testing, and immunocytochemistry were performed. Results The results were as follows: (1) The ERG showed a profound loss of the b-wave amplitude and a “negative” b-wave characteristic of congenital stationary night blindness; (2) a central scotoma and peripheral constriction were identified on Goldmann visual field tests; (3) as in other patients with MAR, bipolar cells in human and rat retinas were immunolabeled with this patient’s serum; and (4) a previously unsuspected focus of metastatic melanoma was discovered. Conclusions Recognition of this condition may help to identify an occult focus of metastatic melanoma.

A Case of Primary Choroidal Melanoma in a Patient With Previous Cutaneous Melanoma-Reply

In reply We thank Dr Abramson and Ms Servodidio for their interest in our article.1We had several reasons for describing this patient with a history of cutaneous melanoma that was excised 7 years prior to the development of a choroidal melanoma. The main reason was to analyze the difficulties that arise in the differential diagnosis between 2 primary tumors vs metastatic disease. We discussed the fact that the ocular tumor was seen as a single choroidal nodule 7 years after the cutaneous melanoma had been removed. In addition to the absence of systemic disease, this strongly suggests that this patient had 2 primary tumors. We also discussed the value of immunohistochemical markers, particularly S100-β, as a possible tool to aid in the histopathological differential diagnosis between primary and metastatic choroidal melanomas. Abramson and coworkers2described a 51 -year-old man who had dysplastic nevus syndrome or B-K mole

Laryngeal mucosal malignant melanoma. A clinicopathologic, immunohistochemical, and ultrastructural study of four patients and a review of the literature.

Primary laryngeal mucosal malignant melanomas are uncommon tumors that morphologically are readily confused with more common types of laryngeal cancer. Four cases of primary laryngeal mucosal malignant melanoma were identified from the files of the Otolaryngic Tumor Registry-Armed Forces Institute of Pathology. Clinical records were available for all four cases. Paraffin blocks or unstained slides were available for three of the four cases. The light microscopic features were evaluated in all cases. Immunohistochemistry was performed in three cases; electron microscopic analysis was performed in two cases. Follow-up data was available in three of the four cases. The patients were all males and ranged in age from 35 to 84 years. The clinical presentations included hoarseness, hemoptysis, dysphagia, and airway obstruction, with complaints ranging from 1 to 8 months. The sites of involvement included the supraglottic larynx and the right true vocal cord. A history of cutaneous melanoma or of a melanoma of another site was not reported for any of the patients. Histologically, the tumors were invasive and composed of a pleomorphic epithelioid cell population of malignant cells. Malignant spindle-shaped cell could also be identified. The presence of melanin was identifiable by light microscopy in two cases; Fontana stains confirmed the presence of melanin in the other two. The immunohistochemical findings showed diffuse immunoreactivity with S-100 protein and HMB-45. There was no immunoreactivity with cytokeratin. The specimen of one patient demonstrated focal immunoreactivity with chromogranin. Electron microscopic features included the presence of premalonosomes or melanosomes. Total laryngectomy was the treatment of choice supplemented with radiotherapy. Follow-up information was available for three patients and all three died of metastatic disease within 36 months of diagnosis. Metastasis occurred to the brain, lungs, spine, and regional lymph nodes. The fourth patient was lost to follow-up. Laryngeal mucosal malignant melanoma is an uncommon neoplasm that clinically and pathologically simulates more conventional types of laryngeal cancers. The light microscopic, immunohistochemical, and electron microscopic findings confirm the diagnosis. Aggressive management is indicated, as these tumors disseminate widely and are rapidly fatal.