Discussion
Cutaneous manifestations are not uncommon in leukemia patients and can have a number of causes, including paraneoplastic cutaneous manifestations, such as pyoderma gangrenosum and Sweet syndrome; infection; cutaneous toxicities from antineoplastic agents; and LC.2 Leukemia cutis can be confused with other skin lesions in leukemia patients; diagnosis requires biopsy.2,9
We analyzed clinical characteristics and prognosis of 46 patients with LC over a 17-year period. To the best of our knowledge, this is the largest study of LC patients published in the United States. A similar study by Kang et al7 analyzed 75 patients in Korea; however, the incidence of LC among different types of leukemia in the Korean population cannot be applied to Western countries. We did compare the clinical characteristics of our cohort of patients to those reported by Kang et al7 and other studies including a smaller number of patients.
In this study, the male to female ratio was 1.3 to 1 compared to the 2:1 ratio reported by Kang et al.7 The mean age of leukemia diagnosis among our patients was 58 years, which is notably older than the mean age previously reported.7 In this cohort, 4 patients (8.7%) were 34 years or younger, including 1 infant aged 8.5 months; 24 (52.2%) were aged 35 to 64 years; and 18 (39.1%) were 65 years and older.
Consistent with other studies,2,5,7 the most common type of leukemia in patients who developed LC was AML (80%). Among AML patients, the mean age at AML diagnosis (59.8 years) was notably younger than the reported US average age of patients who had a diagnosis of AML (68 years).10 Gender breakdown was slightly different than US statistics: 63% of AML patients in our group were male, whereas AML is only slightly more common among men in the United States.10
Clinically, skin lesions observed most commonly were (in decreasing order) papules, nodules, macules, plaques, and ulcers. Papules (38%) were the most common lesion overall in our study, which differed from the Kang et al7 report in which nodules were the most common. Nodules (31%) were the second most common LC morphology among our patients. Among AML patients, papules were seen in 56% of patients (18/32); nodules were seen in 44% (14/32). The extremities (when combined together) were the most common location of LC lesions (46% [arms, 24%; legs, 22%]); the trunk was the second most common body region (31%). Our study did not find a difference among most common LC anatomic sites compared to other studies.5,7 Less common sites in our cohort included the head, scalp/ears, neck, hands, mucosa, and feet. All body sites were represented, including ocular and oral mucosa and groin, a finding that underscores the importance of complete and comprehensive skin examinations in this patient population. The terms erythematous and violaceous were used to describe the color of most lesions (88%), which commonly presented as multiple lesions (84%) and often were asymptomatic (84%).
It has been reported that, first, in most cases of LC, the condition develops in patients who have already been given a diagnosis of leukemia and, second, simultaneous manifestation of systemic leukemia and LC is less common.11,12 Leukemia cutis also can precede peripheral or bone marrow leukemia (known as aleukemic LC).1,13 Two AML patients (4.3% [2/46]) in this study met criteria for aleukemic LC because they had LC at the same time as negative bone marrow biopsy, which is consistent with a prior report that aleukemic LC can affect as many as 7% of patients.1 Our results differed slightly from prior studies in that most of our patients had LC as one of the presenting manifestations of their leukemia.3,7
Regardless of leukemia type, patients were likely to die within 1 year of LC diagnosis, on average, which is consistent with prior reports.7,11,12 However, the time between diagnosis of LC and death varied greatly among our patients (range, 12 days to 4.1 years). From 2007 to 2013, the 5-year relative survival rate overall for leukemia patients in the US population (by type) was 86.2% (CLL), 71.0% (ALL), 68.0% (CML), and 27.4% (AML).14 Compared to these national statistics, the relative survival rate in LC is poor, with patients who have AML surviving, on average, less than 8 months from time of leukemia diagnosis, whereas ALL and CLL patients survive less than 6 months.
When LC is a late presentation of B-cell CLL or when it presents as myeloid leukemia, blastic transformation (Richter syndrome), or T-cell CLL, it is occasionally associated with poor prognosis, though LC does not affect survival.15-17 In a study of the association of LC with survival in AML, 5-year survival among 62 AML patients with LC was 8.6%, shorter than 28.3% among the 186 matched patients with AML without LC.18 Similarly, the estimated 5-year survival for all patients with AML, according to Surveillance, Epidemiology, and End Results Program data (2007-2013), was 27.4%.14 Based on those results, LC might be a good prognostic indicator in patients with AML.
Conclusion
This study characterized the clinical presentation of LC, which is highly variable in appearance, symptoms, distribution, and stage of leukemia at presentation. In our study cohort, LC most commonly presented as asymptomatic erythematous or violaceous papules or nodules in older male AML patients at leukemia diagnosis. Given such wide variability, dermatologists and oncologists need to keep LC in the differential diagnosis for any new skin lesion and to have a low threshold for performing skin biopsy. Complete and thorough skin examinations should be performed on leukemia patients throughout the course of their disease to identify LC early so that treatment can be implemented in a timely fashion at initial diagnosis, first sign of relapse, or change in disease state.