Melanoma of unknown primary

Abstract

Formally described in the 1960s, melanoma of unknown primary (MUP) is characterized by the finding of metastatic melanoma within the lymph nodes, subcutaneous tissues, and other distant sites without an evident primary lesion. The most likely hypothesis of its etiology is an immune-mediated regression of the primary after metastasis has occurred.In addition, patients with MUP appear to have equivalent or better outcomes compared with patients with known primaries of a similar stage. K E Y W O R D S malignant melanoma, melanoma occult primary, melanoma regression, unknown primary 1 | INTRODUCTION Melanoma incidence has increased steadily over the last three decades. Over 90 000 new cases are estimated to be diagnosed in the year 2018 in the United States. 1 The vast majority of cases are cutaneous melanoma, but melanoma can also occur in extracutaneous locations, such as the eyes or mucous membranes. 2 Although more than 90% of cases are comprised of melanomas with a known primary site (MKP), occasionally it is discovered first as a secondary deposit within lymph nodes, subcutaneous tissues, or other organs without a clearly evident site of origin. The first diagnosis of melanoma of unknown primary (MUP) dates back to 1917. 3 Pack et al 3 described a series of 1,190 patients treated at Memorial Hospital between 1917 and 1950, of which 29 (2.4%) patients were classified as having an occult primary. Compared with other patients with melanoma, patients diagnosed with MUP were initially reported to have especially poor outcomes. While the overall 5-year recurrence-free survival was 21.4%, only one patient with MUP was cured. The authors wrote that "the patient defies all laws and expectations by continuing to live" 14 years after initial axillary dissection for lymph node metastasis. Das Gupta 4 formally described the entity of MUP in 1963. His proposed diagnostic criteria excluded patients who had any of the following: a history of orbital exenteration or enucleation; a history of excision or removal of any mole, birthmark, freckle, chronic paronychia, or skin blemish; scar in the skin drained by the nodal basin containing metastatic melanoma; and an incomplete physical examination, which also included ophthalmoscopy and examination of the anus and genitalia. 2 | DIAGNOSTIC CRITERIA Few studies use the full diagnostic criteria set forth by Das Gupta to define MUP. 5-10 In a systematic review, Kamposioras et al 11 reported that only 16% of published peer-reviewed studies of MUP used the original Das Gupta criteria to define cases of unknown primaries. The majority of studies make the diagnosis of MUP based on history, physical examination, pathology, and imaging, resulting in heterogeneity and variations in how MUP is defined. Studies typically vary in the completeness of physical examination required and the exclusion of patients with previously existing skin lesions. For example, Wong et al and Katz et al 12,13 defined patients as having MUP only if they had a documented thorough skin examination and did not have an...

Neoadjuvant therapy with vemurafenib in Horner's syndrome as a very rare first diagnosis of a malignant melanoma of unknown primary

“…In rare cases the primary lesion is located in the ear, eye, urethra or intestinal mucosa [1]. However, the most favored assumption is immune-mediated degradation of the primary site, while metastases are not affected [2].…”

Patients with melanoma of unknown primary show better outcome under immune checkpoint inhibitor therapy than patients with known primary: preliminary results

“…1,2 Once melanoma has spread into the lymph nodes, or even visceral organs and the brain, it remains a life-threatening disease despite the advent of molecular targeted or immunotherapies. 1,2 Melanoma of unknown primary (MUP) [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] represents an unusual subtype of melanoma which was reported to be about 2-9% of melanoma of known primary (MKP) at all stages. 3 Some of the literature in the different geographic regions demonstrated better overall survival of MUP than of MKP.…”

“…15 Other publications, however, reported an equal or even worse clinical outcome for patients with MUP when compared to MKP with comparable stage of disease. [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Hence, the prognosis of patients with MUP compared to MKP patients is still unclear and likely depends on the clinical scenario investigated. A 5-year overall survival rate of MUP before the era of the immune checkpoint inhibitor was reported to range from 8% to 18% with the most common metastatic sites in lymph nodes and gastrointestinal tract.…”

Neoadjuvante Therapie mit Vemurafenib bei Horner‐Syndrom als sehr seltene Erstdiagnose eines CUP‐Syndroms bei malignem Melanom

“…Aktuell wird jedoch die Hypothese favorisiert, nachdem ein Primarius immunvermittelt abgebaut werden kann, während Metastasen vom Immunsystem nicht erkannt werden [2]. In seltenen Fällen findet sich der Primarius im Ohr, Auge, in der Urethra oder der Darmschleimhaut.…”