This review will explore various leukemia-related cutaneous findings and discuss the diagnosis and management of these conditions.
Leukemia is a malignant disorder that affects the blood cells that arise in the bone marrow and other blood-forming organs that can cause a variety of complications. Cutaneous findings are common and can be an important manifestation of leukemia and include conditions such as leukemia cutis, blastic plasmacytoid dendritic cell neoplasm (BPDCN), and paraneoplastic syndromes. This review will explore the various leukemia-related cutaneous findings and discuss the diagnosis and management of these conditions.
Leukemia cutis is a rare complication of leukemia in which cancer cells infiltrate the skin resulting in distinctive skin lesions. It can occur at any age and can affect both males and females, although it is more common in children than adults. It is more frequently seen in individuals with acute myeloid leukemia (AML) than chronic myeloid leukemia (CML)1. The prevalence of leukemia cutis in AML ranges from 10-15%, depending on the subtype of AML2.
Leukemia cutis can present in various ways, including single or multiple patches, papule, nodules, or plaques of varying size3. The color of the lesions can vary and may appear yellow, brown, red, or purple. These lesions can be itchy and painful, and may occur anywhere on the body. The trunk, extremities, and head are equally affected, but palmoplantar surfaces and the oral mucosa involvement are less common4.
The diagnosis of leukemia cutis typically requires a skin biopsy. The evaluation of the biopsy sample includes an assessment of the pattern of distribution of the tumor cells, as well as the cytological and immunohistochemical characteristics of the cells. On histology, most cases show a perivascular, periadnexal pattern of involvement, a dense diffuse or nodular infiltrate involving the dermis and subcutis1. Stromal fibrosis is also common1. The histological appearance of the tumor cells may vary and may not necessarily correlate with the clinical appearance of the lesion5. Peripheral blood and bone marrow tests may also be considered, along with the overall clinical course of the disease.
The primary goal of treatment for leukemia cutis is to treat the underlying leukemia. This may involve chemotherapy, radiation therapy, or other forms of cancer treatment3. In some cases, radiation therapy may be used to target the cancer cells in the skin specifically. The prognosis for leukemia cutis can vary depending on the type of leukemia and the extent of the skin involvement. The presence of systemic manifestations is often an unfavorable factor in the prognosis6-8.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare, clinically aggressive hematologic malignancy that most commonly presents with skin lesions. Although the exact incidence of BPCDN is unclear, it is estimated to occur in about 0.04 cases per 100,000 people9. It can occur at any age and any gender, but it is more commonly diagnosed in older men with about 75% of those affected being male and the median age at diagnosis being between 60-70 years old10.
Over 80 percent of cases of BPDCN present with skin lesions, regardless of whether there is bone marrow involvement or leukemic dissemination11. The skin lesions associated with BPDCN, can be single or widespread and can take various forms, such as brown or purple nodules, bruise-like brown to purple infiltrated patches and plaques, and disseminated mixed lesions12. In rare cases, BPDCN may present without any evidence of skin involvement.
Skin biopsy with histology and immunophenotype is important in making a diagnosis, in additional to its clinical manifestations. Skin biopsy of a BPDCN case demonstrates infiltrate of medium-sized cells that spare the epidermis but can extend to the subcutaneous fat. Immunophenotype should be positive for CD4, CD56 and several other plasmacytoid dendritic cell associated markers, such as CD123 and TCL110.
Traditionally, BPDCN is treated with chemotherapy regimens for acute leukemia, although the overall survival generally remains poor. Allogeneic stem cell transplant can be considered in their first remission to improve overall survival rate. FDA approved Tagraxofusp in 2018 as the first drug with a specific FDA indication for BPDCN treatment13. New drugs targeting CD123 and BCL-2 are currently under investigating, and on the horizon as well14.
Paraneoplastic syndromes are a group of rare disorders that are triggered by abnormal immune system response to leukemia or other types of cancer. Leukemia-related paraneoplastic syndromes can manifest in the skin as inflammation with erythematous or violaceous skin eruptions as a primary feature.
Sweet syndrome, also called acute febrile neutrophilic dermatosis, is a rare skin condition that manifests as red, tender papules or nodules on the upper extremities, face, and neck. Systemically, it is often accompanied by fever and neutrophilia. Malignancy-associated sweet syndrome can occur as a paraneoplastic syndrome and is commonly associated with acute myelogenous leukemia. Malignancy-associated sweet syndrome occurs with similar frequency in men and women, and it is often temporally closely associated with the discovery or relapse of cancer. Skin biopsy may show diffuse infiltrate of mature neutrophils in the dermis or subcutaneous fat. Management generally involves treating the underlying malignancy, while corticosteroids, potassium iodide, and colchicine may also be helpful in symptom management15.
Erythroderma, or exfoliative erythroderma syndrome, is a condition characterized by widespread redness and scaling of the skin. While the most common causes are atopic dermatitis or psoriasis, erythroderma has also been linked to cutaneous T-cell lymphoma and acute myeloid leukemia. It is important to perform immunohistochemistry and T-cell receptor gene rearrangement studies to investigate the underlying cause of erythroderma. In many cases, the erythroderma will resolve after treating the underlying malignancy. Topical corticosteroids and antihistamines may be helpful in relieving symptoms16.
Paraneoplastic autoimmune multiorgan syndrome, previously known as paraneoplastic pemphigus, is a very rare disorder that is characterized by a polymorphous cutaneous eruption, including vesicles and bullae, erosions, patches, papules, and plaques. This condition predominantly affects males between the ages of 45 and 70, although it can also affect the pediatric population. A skin biopsy with immunofluorescence and immunoprecipitation to check for autoantibodies is typically required for diagnosis. Paraneoplastic autoimmune multiorgan syndrome is commonly associated with non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and other hematologic-related neoplasms. Respiratory failure is a common cause of death in these cases. Treatment for this condition is challenging, and the most favorable outcomes have been observed in cases with complete resection of the tumor. Corticosteroids, alemtuzumab, and acetylcholinesterase inhibitors may be beneficial in the pharmacological management of this condition17.
Cutaneous findings can be an important manifestation of leukemia and may include conditions such as leukemia cutis, BPDCN, and various paraneoplastic syndromes. However, there are other cutaneous findings that can occur in leukemia patients that are not directly related to the leukemia itself. For example, skin infections due to compromised immune system and drug side effects from cancer treatment can also cause skin abnormalities in these individuals. It is important for healthcare professionals to consider these other potential causes when evaluating and managing cutaneous lesions in leukemia patients.
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