AUTHOR AND EDITOR INFORMATION

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INTRODUCTION

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• Clinical
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• Miscellaneous
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Background

Leukemia cutis is the infiltration of neoplastic leukocytes or their precursors into the epidermis, the dermis, or the subcutis, resulting in clinically identifiable cutaneous lesions.

The dermatologist is instrumental in the diagnosis of leukemia cutis. Accurate diagnosis has tremendous prognostic significance and may establish a diagnosis in cases in which leukemia cutis is the harbinger of a systemic leukemic process. This is called aleukemic leukemia cutis. Additionally, a diagnosis of leukemia cutis portends a poor prognosis and strongly correlates with additional sites of extramedullary involvement. This can alter the appropriate treatment regimen for a patient.

Pathophysiology

All types of leukemias result from the abnormal development of leukocytes in the bone marrow. Maturational arrest occurs, and a proliferative, clonal population of cells result. A variety of defects promote the clonal expansion of leukemic cells. These defects include an abnormal proliferative potential, defects in terminal differentiation, and defective apoptosis. The increased proliferative potential is caused by the activation of oncogenes or the inactivation of tumor suppressor genes. Leukemia cutis is thought to result from a local proliferation of the leukemic cells within the skin.

The pathophysiology underlying the specific migration of leukemic cells to the skin is not clear. In the case of human T-cell leukemia virus type I (HTLV-I)–induced leukemia, it may be due to the abundant expression of the CC chemokine receptor 4 (CCR4) on the cell surface of the leukemic cells. The ligands thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) are present in the skin and may explain the predilection of adult T-cell leukemia to involve the skin. Evidence also suggests that the presence of T-cell–related antigens on the cell surface of leukemic cells in acute monocytic leukemia (AML-M5) in patients with leukemia cutis may promote selective homing to the skin. Additionally, one small study of 18 cases of myelomonocytic leukemia cutis patients showed cutaneous lymphocyte-associated antigen (CLA) staining in 14 (78%) of 18 cases. The presence of CLA may confer a specific tropism to the skin in these leukemic cells.

Frequency

United States

Because leukemia cutis is a relatively rare condition and because it may manifest in a variety of leukemia subtypes, the exact overall incidence of leukemia cutis is unclear. For the various subtypes, the approximate incidences are listed in the table below.

Although adult T-cell leukemia/lymphoma (ATLL) is exceedingly rare in the United States, a disproportionate percentage of patients develop leukemia cutis. The rate of seroprevalence of HTLV-I in volunteer blood donors in the United States is 0.02%. Of the individuals infected with HTLV-I, only 2-4% develop ATLL. Acute myelogenous leukemia (AML) shows the second highest rates of leukemia cutis. The French-American-British (FAB) classification divides AML into 8 main subtypes M0 to M7, based on the morphology and the state of differentiation of the leukemic cells. Acute myelomonocytic leukemia (AML-M4) and AML-M5 have the highest rates of skin involvement of all the subtypes and are reported to be as high as 30%.

The incidence of leukemia cutis also appears to be high among children, and cases of leukemia cutis have been documented in as many as 25-30% of infants with congenital leukemia. Most of these patients have myelogenous leukemia. In congenital leukemia, leukemia cutis does not worsen the prognosis.

In most cases of leukemia cutis, systemic disease precedes the development of skin lesions. However, in as many as 7% of patients with leukemia cutis, localized disease occurs prior to bone marrow infiltration and systemic symptoms (aleukemia cutis or primary extramedullary leukemia [EML]).

Table 1. Incidences of Types of Leukemia

International

In general, the international incidence of leukemia cutis is thought to be similar to that in the United States. One study by Agis et al in Vienna showed a prevalence of 2.9-3.7% for AML. This is a figure similar to the rate determined by Baer et al in the United States.

The exception to this rule would be the prevalence of HTLV-I–induced ATLL, which is significantly higher in the Caribbean and Japan. In Japan, 6-37% of the population is infected with HTLV-I in endemic areas. Of these, 0.5 per 1000 women and 1.5 per 1000 men will develop ATLL. In the Caribbean, 3-6% of the population is seropositive for HTLV-I. Reportedly, the rate of cutaneous involvement in ATLL ranges from 40-70%.

Mortality/Morbidity

In general, leukemia cutis is a poor prognostic sign. Several studies indicate that, in the presence of leukemia cutis in AML or CML, the disease course is aggressive and the length of survival is short.

• A study by Kaddu et al showed an average survival time in AML to be 7.5 months and in CML, 9.4 months.
• Another study by Baer et al showed that of 18 patients with leukemia cutis in AML, 90% had other sites of extramedullary involvement, and, in 40% of these patients, the meninges were involved.
• In a smaller case series by Shaikh et al with only 5 patients with AML, all 5 died within 6 months of their diagnosis of leukemia cutis. One series by Su et al of 16 patients with CLL showed a mean survival time of 16 months, with 88% of the patients dying within 1 year.

Race

Although specific racial, sexual, and age predilections for the subtypes of leukemia exist, no data regarding any of these factors in leukemia cutis are available.

CLINICAL

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History

In a patient with a previous diagnosis of leukemia and possible leukemia cutis, the history is important to attempt to identify other potential sites of extramedullary involvement. As many as 90% of patients with leukemia cutis also have other extramedullary involvement, and as many as 40% of patients have meningeal involvement. In patients with possible leukemia cutis as the presenting sign of systemic leukemia, the history may be essential in narrowing the differential diagnosis.

• The pancytopenia caused by leukemia results in a variety of manifestations. Symptoms of anemia, including pallor, lethargy, and dyspnea may be prominent. A recent history of easy bleeding and bruising is suggestive of thrombocytopenia.
• Neutropenia predisposes one to bacterial, viral, or fungal infections. These infections may present in the skin, the gingiva, the urinary tract, or the lungs. Any of these infections may be accompanied by fevers.
• • Aspergillus and Fusarium organisms may appear at sites of trauma, such as central lines or intravenous insertion sites, or as disseminated nodules and ulcerations. Atypical mycobacterium type IV also cause infections in these patients.
  • Infiltration of leukemic cells into a variety of organs produces different symptoms in each organ system. Nausea, abdominal fullness, early satiety, and constipation are several symptoms that can occur as a result of hepatomegaly or splenomegaly, which are common in leukemia.
  • CNS involvement by leukemic cells may be associated with cranial nerve palsies, seizures, altered mental status, or headache with nausea due to increased intracranial pressure. An unusual presentation of leptomeningeal infiltration by leukemic cells is the numb chin syndrome. Patients complain of loss of sensation or altered sensation in the chin area, without any evidence of a primary dermatosis or a history of preceding trauma.
  • Patients may complain of bone and joint pain. Infiltration of the periosteum/bone results in painful lesions and, in certain cases, pathologic fractures. Joint swelling and arthritis may be secondary to gouty arthritis from hyperuricemia.
• Leukostasis can occur in patients with a significant amount of circulating leukemia cells. Clinical manifestations vary from CNS symptoms, respiratory distress from lung involvement, or priapism. Rare reports describe leukemic vasculitis in which leukemic cells actually infiltrate the blood vessel walls.
• The specific lesions of leukemia cutis are most often asymptomatic. No pruritus, pain, or tenderness is associated. The exceptions to this are CLL and HTLV-I–induced ATLL, in which significant pruritus can occur.
• • A typical presentation of acute ATLL includes a history of fever, chills, and lethargy. Many cases of associated dermatitis, which may be extremely pruritic, have been described.
  • Other symptoms that may be reported include abdominal pain, cough, and diarrhea. Patients may complain of abdominal fullness due to the hepatosplenomegaly or ascites, which may be present. Patients may also complain of swollen lymph nodes.

Physical

As mentioned briefly in History, pallor; hepatosplenomegaly; nonspecific findings (eg, purpura, petechiae); drug reactions, including leukocytoclastic vasculitis; and opportunistic infections, particularly thrush, disseminated zoster, or severe and atypical presentations of herpes simplex may be present.

Many cutaneous manifestations of chemotherapeutic agents may occur. Some of the most common include alopecia, stomatitis, acral erythema, and hyperpigmentation of the nails or the mucous membranes. Other less common chemotherapy reactions include neutrophilic eccrine hidradenitis and eccrine squamous syringometaplasia. These present as localized or generalized erythematous macules, papules, or plaques.

Some inflammatory cutaneous reactions may occur in patients with leukemia, but they are not a direct result of infiltration of leukemic cells into the skin. These include acute febrile neutrophilic dermatosis (secondary to AML or granulocyte colony-stimulating factor [GCSF]), graft versus host disease, and persistent arthropod bite–like reaction (most commonly seen in CLL). These lesions are included in the differential diagnosis of leukemia cutis.

• More specific cutaneous lesions of leukemia cutis are typically papules and nodules; indurated plaques, hemorrhagic plaques, perifollicular acneiform papules, macules, ulcers, bullae, and palpable purpura are less frequent. The lesions can range from red-brown to violaceous, or plum. The lesions may be seen in any type of leukemia causing leukemia cutis.
• Patients may present with single or multiple nodules in the absence of any systemic findings. The tumors are called granulocytic sarcoma or primary EML. These tumors may appear greenish. They have been aptly called chloromas because of the green pigmentation caused by myeloperoxidase within the myeloid cells.
• More unusual lesions vary depending on the underlying leukemia.
• • AML-M4 and AML-M5 have characteristic gingival hypertrophy as a result of leukemic infiltration. This may be present in as many as 50% of patients with these subtypes of leukemia.
  • In acute myelomonocytic leukemia, leukemia cutis may manifest as leonine facies.
  • Juvenile CML may show figurate or arciform lesions.
  • Two reports describe leukemia cutis as the presenting sign of a transformation of myelodysplastic syndrome into AML. One described leukemic infiltrates on the hands, the other described stasis dermatitis, which was, in fact, leukemia cutis.
  • One case report of hairy cell leukemia with leukemic macrocheilitis and Melkersson-Rosenthal syndrome has been reported.
  • Fingertip hypertrophy consisting of leukemic infiltrates of CLL has also been described. B-cell CLL has manifested as symmetrical eyelid leukemia cutis. A case series of 6 patients with B-cell CLL demonstrated leukemia cutis in areas typical of Borrelia burgdorferi–induced pseudolymphomas, namely earlobes, nipples, and scrotum. These cells showed aberrant CD20⁺/CD43⁺ phenotype, and 4 of the 6 tumors demonstrated B burgdorferi DNA by polymerase chain reaction. CLL also may manifest as erythroderma or bullous lesions.
  • Other unusual manifestations include erythema nodosum, erythema annulare centrifugum, pyoderma gangrenosum, lesions mimicking urticaria, urticaria pigmentosum, guttate psoriasis, chronic paronychia, subungual leukemia cutis, and macular erythema.
  • The first case of leukemia cutis manifesting as a Sister Mary Joseph's nodule was reported in a case of acute promyelocytic leukemia (APL). Leukemia cutis in APL is rare; however, the patient was previously treated with all trans retinoic acid, a factor that increases the chance of extramedullary involvement with relapse.
• Leukemia cutis may occur within established scars and within recent areas of trauma, including Hickman catheter sites, sites of burns, decubitus ulcers, herpes simplex virus (HSV) scars, or zoster scars. Plasma cell leukemia cutis has been reported to occur in recent puncture sites. Leukemia cutis at a site of trauma has been reported in one case of Burkitt-type ALL (L3ALL).
• In ATLL, 60% of patients have peripheral lymph node enlargement, 26% have hepatomegaly, 22% have splenomegaly, and 39% have skin lesions.

Causes

Both a genetic component and an environmental component appear to be involved in many leukemias. A variety of well-characterized chromosomal translocations result in specific leukemic syndromes.

Patients with Down syndrome have an increased risk for both megakaryoblastic leukemia and pre–B-cell leukemia.

Other genetic syndromes, including Bloom syndrome, Klinefelter syndrome, Wiskott-Aldrich syndrome, and Fanconi syndrome, have shown an increased incidence of leukemia.

CLL shows some familial tendency in approximately 20% of CLL cases.

Several genetic mutations lead to an asymmetric maturation of stem cells and result in a single clonal expansion of a severely defective stem cell. The specific mutations and phenotypic changes resulting from genetic aberration determine the subtype of leukemia. After the development of the leukemic clones, a tissue-selective homing process that leads to the infiltration of malignant cells into the epidermis, the dermis, the subcutaneous fat, and the mucosa occurs.

The molecular basis responsible for the development of leukemia cutis is not yet defined. However, initial cytogenetic studies are starting to provide insightful information that would lead to a better understanding in the pathophysiology of leukemia cutis. Prior studies have demonstrated that as many as 50% of patients with AML-M4 or AML-M5 develop leukemia cutis and other forms of EML. Karyotypic studies of leukemic cells have demonstrated the translocation of chromosomes 8 and 21 t(8;21) in these subtypes of AML. A strong association exists between aneuploidy of chromosome 8 and leukemia cutis. Other cytogenetic abnormalities noted in leukemia cutis are chromosome 3 translocations and t(6;9)(p23;q34). Chloromas, primary EMLs are associated with t(8;21), t(9;11) and inv(16) translocations. Identification of proteins coded by specific genes located in those chromosomes would assist in defining factors responsible for the development of leukemia cutis.

Environmental exposures may increase the risk of leukemia. Benzene exposure increases one's risk for AML. Ionizing radiation exposure may increase the risk of leukemia as well, particularly AML, CML, and ALL. Alkylating agents used in chemotherapy cause an increased risk of subsequent AML. The use of all trans retinoic acid to treat APL may predispose a patient to increased risk of extramedullary involvement, including leukemia cutis, which is otherwise rare in APL. Other leukemias may be caused by viral infection. These include ATLL, caused by HTLV-I and acute B-cell leukemia and large granular lymphocytic leukemia, which may be the result of Epstein-Barr virus infection.

DIFFERENTIALS

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Other Problems to be Considered

Vasculitis
Viral exanthema
Non-Hodgkin lymphoma
Purpura

WORKUP

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Lab Studies

• A complete blood count is performed to assess the degree of anemia, thrombocytopenia, and neutropenia or leukocytosis. If these measurements are low, supportive treatments may be given or precautionary measures may be initiated.
• A peripheral blood smear to look for circulating leukemic cells and to assess for disseminated intravascular coagulation should be performed.
• Chemistry profile is necessary to assess baseline levels for BUN and creatinine prior to initiation of chemotherapy and to monitor these levels during chemotherapy as a reflection of renal function.
• • Most patients with leukemia have an elevated lactic dehydrogenase (LDH) level and an elevated uric acid level. Elevation of LDH is often a poor prognostic sign.
  • Liver function tests and BUN and creatinine determinations are necessary prior to the initiation of therapy because many chemotherapeutic agents may adversely affect either renal function or hepatic function. Additionally, some agents, such as methotrexate, may be contraindicated in individuals with hepatic dysfunction.
  • Some leukemias may have other electrolyte abnormalities, including hypokalemia, hypocalcemia, and/or hypomagnesemia. In ATLL, hypercalcemia occurs in approximately one third of all patients.
• Appropriate cultures should be obtained in patients with fever or signs of infection.

Imaging Studies

• Imaging studies should be obtained based on the patient's symptoms to determine the extent of extramedullary involvement of leukemia or potential sites of infection.
• Some imaging studies may be needed to assess the baseline status prior to chemotherapy administration; for example, echocardiography may be performed prior to the initiation of chemotherapy.
• In all the leukemias, chest radiography may show evidence of an infection, such as pneumonia. In some cases of T-cell ALL, mediastinal lymphadenopathy may be present.
• Typical hepatomegaly and splenomegaly may be imaged by using a liver/spleen scan. Most often, these findings are so obvious in cases of CLL, hairy cell leukemia, and ATLL that imaging is unnecessary because the organs are easily palpable. In milder cases, liver or spleen scan or ultrasonography may reveal more subtle organomegaly.
• Computed tomography of the chest, the abdomen, or the pelvis is generally not required for staging purposes. However, be careful not to miss lesions, such as obstructive uropathy or airway obstruction, that are caused by lymph node compression on organs or internal structures.

Other Tests

• Cytogenetic studies and flow cytometry on peripheral blood may be performed.
• In cases of ATLL, studies to assess monoclonal integration of the HTLV-I genome into genomic DNA are helpful.

Procedures

• Skin biopsy
• • Skin biopsy with appropriate immunohistochemical staining is the key to diagnosing aleukemic leukemia cutis or identifying leukemia cutis, a sign of extramedullary extension of the leukemia, and a poor prognosis. This diagnosis will likely impact the most appropriate course of treatment.
  • Bone marrow aspiration and biopsy are the definitive diagnostic tests for the diagnosis of systemic leukemia.
  • Bone marrow aspirates should be stained with either Wright stain or Giemsa stain for morphologic analysis.
  • In addition, slides should be stained with immunocytochemical stains to determine the cell lineage and the degree of maturation.
  • Bone marrow samples should be sent for cytogenetic and flow cytometric studies.
• Immunophenotyping
• • Immunophenotyping of infiltrates with specific markers is a valuable adjunct in confirming the diagnosis of leukemia cutis and in differentiating specific from nonspecific cutaneous infiltrates. Specific markers include the following: CD3 (T cells), CD45RO (mature T cells), CD45/LCA (leukocyte common antigen) (lymphocytes, monocytes), CD43 (T cells, monocytes, and granulocytes), CD20 (B cells), CD30 (activated T cells), CD68 (monocytes), and lysozyme (granulocytes, monocytes) (see Table 2 below).

    Table 2. Recommended Immunohistochemical Stains For Leukemia Cutis

    Cell Lineage	CD Antigen Marker
    T cell	CD45 (LCA) strongly positive CD45RO usually strongly positive CD3 positive but only scattered
    B cell	CD20 strongly positive but scattered in normal B cells, weakly positive or negative in abnormal small B cells, positive in abnormal large B cells CD43 usually negative
    Granulocytes	Lysozyme strongly positive in well and poorly differentiated granulocytes Chloroacetate esterase positive in well-differentiated granulocytes CD68 usually negative in all granulocytes
    Monocytes	Lysozyme strongly positive in well and poorly differentiated monocytes Chloroacetate esterase usually negative CD68 positive in well-differentiated monocytes

  • Chloroacetate esterase stains CML and most subtypes of AML but not AML-M4. However, lysozyme should stain all forms of AML and CML.
  • AML-M4 types express CD43 and CD68 as well. CD43, CD45, and CD15 are positive in almost all types of AML-M5 and AML-M4.
  • B-cell CLL cells do not typically express CD20.
  • In T-cell CLL, CD45RO and CD3 are either negative or only weakly positive.
  • ATLL cells stain with CD3, CD4, and CD25. CD8 is most often negative.
  • Hairy cell leukemia cells, which are of the B-cell lineage, stain strongly with tartrate-resistant acid phosphatase. Hairy cells have a mature B-cell phenotype and express immunoglobulin light chains and B-cell antigens, such as CD19, CD20, and CD22, but not CD21. Monoclonal Bly-7 has a high sensitivity and specificity for hairy cell leukemia. CD22 stains hairy cell leukemia more prominently than normal B cells.

Histologic Findings

The histologic findings in leukemia cutis vary depending on the subtype of leukemia. Typically, little epidermal involvement with an underlying Grenz zone is present. A dermal infiltrate of leukemic cells, which is often perivascular and periadnexal, is present. Collagen bundles may be prominently separated by leukemic cells. The leukemic cells may also infiltrate along the fibrous septae of the subcutaneous fat. The cells may be seen in the lumina of the blood vessels as well as infiltrating the walls, producing a leukemic vasculitis.

Cells in AML are large with an oval, vesicular nucleus and basophilic cytoplasm.

In CML, a variety of cells at varying degrees of maturation are present. Eosinophils may be present.

ALL shows medium-to-large blast cells, with a high nuclear-to-cytoplasmic ratio.

CLL shows small, more uniform, mature lymphocytes. These have dense nuclear chromatin. T-cell CLL may show epidermotropism, as do other T-cell leukemias.

Monocytic leukemia may be confused with large cell lymphoma because of the large nucleus with fine chromatin and prominent nucleoli. The nuclei are often indented or kidney shaped and slightly basophilic in appearance. Monocytic leukemia often involves the entire dermis and the superficial panniculus.

ATLL cells show an indented to lobulated nucleus, which has led to the term flower cells to describe the morphology. ATLL unlike many of the other leukemic infiltrates often shows epidermotropism. Pautrier microabscesses, as can be seen in mycosis fungoides, may be present.

Hairy cell leukemia, like many other forms of leukemia cutis, infiltrates the dermis and the subcutaneous fat. It too shows prominent periadnexal and perivascular infiltration. The infiltrate consists of monomorphous mononuclear cells. A Grenz zone is typically present.

Staging

Staging is extensively discussed in other articles about each of the subtypes of leukemia elsewhere in the eMedicine Journal.

TREATMENT

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Medical Care

Leukemia cutis is a local manifestation of an underlying systemic disease; therefore, the treatment should be directed at eradicating the leukemic clone by using systemic chemotherapy. The treatment of leukemia should be determined by the subtype of leukemia and by the patient's ability to tolerate a treatment regimen. This is primarily dependent on the overall medical condition of the patient, including any comorbid conditions that may exist. Under certain circumstances, such as resistant or recurrent skin disease, local treatment in the form of electron beam therapy can be used. However, in most of these cases, reinduction systemic chemotherapy must be added unless medically contraindicated by the patient's comorbidity. Refer to Acute Myelogenous Leukemia and Acute Lymphoblastic Leukemia.

Surgical Care

Most patients require central venous catheter placement for chemotherapy delivery, if they do not have one.

Consultations

• Consult a hematologist and an oncologist if the patient presents with aleukemic leukemia cutis.
• Consider a consultation with a radiation oncologist, although chemotherapy with anthracyclines either prior to or concurrent with radiation therapy may cause severe adverse cutaneous reactions. Radiation with cytarabine does not cause adverse reactions.

Diet

If neutropenic, the patient should not consume fresh vegetables or fruit.

Activity

Patients should avoid extremely strenuous activity.

MEDICATION

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The chemotherapeutic regimen chosen depends on the subtype of leukemia. An extensive discussion of specific chemotherapeutic protocols can be found in eMedicine articles on the individual type of leukemia.

Drug Category: Antineoplastic agents

These agents inhibit cell proliferation.

Drug Category: Growth factors

These agents are indicated in patients receiving chemotherapy with signs of infection and neutropenia.

Drug Category: Uricosuric agents

These agents increase the renal clearance of uric acid by inhibiting the renal tubular reabsorption of uric acid.

FOLLOW-UP

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Further Inpatient Care

• Further inpatient care is typically determined by a hematologist or an oncologist.

Further Outpatient Care

• Further biopsies may be performed as required to rule out recurrences, graft versus host disease after bone marrow transplantation (BMT), or unusual infections resulting from immunosuppression.
• Appropriate prophylactic antifungal, antiviral, and Pneumocystis carinii pneumonia (PCP) agents and supportive growth factor treatment are needed.

In/Out Patient Meds

• Refer to the individual articles in the eMedicine Journal regarding appropriate chemotherapeutic regimens for the specific subtype of leukemia.
• In general, most patients on chemotherapy should receive prophylaxis for common infectious agents, including HSV, Candida species, and P carinii. They should also receive symptomatic treatment for mucocutaneous complications of chemotherapy. These treatments include ketoconazole troches (for thrush) and viscous lidocaine alone or a compound containing lidocaine solution, diphenhydramine hydrochloride, and aluminum hydroxide suspension, ie, "magic mouthwash," (for stomatitis) or chlorhexidine and may relieve symptoms. Symptomatic treatment, including topical steroids, mentholated lotions, or topical lidocaine preparations (Lida-Mantle), for medication- or radiation-induced skin eruptions is often helpful. Preparations containing hyaluronic acid or a medication called biafine can speed the healing of skin with radiation damage.

Transfer

• Patients should be primarily cared for by a hematologist and oncologists at a tertiary care medical center.

Deterrence/Prevention

• Patients should avoid crowded public places because of the risk of infection.
• Patients should avoid contact with others who are ill.
• Patients should avoid receiving most live vaccines. This may not apply under special circumstances, such as an actual outbreak of smallpox, during which time the risk of death would be greater than the risk of vaccine-associated adverse events.
• Patients should avoid contact with persons who have been vaccinated with live vaccines.

Complications

• Complications include the following:
• • Infection: As previously mentioned, patients are at risk for a variety of opportunistic infections.
  • Bleeding: Bleeding as a result of thrombocytopenia is common.
  • Reactions to chemotherapy
  • Graft versus host disease: Graft versus host disease following bone marrow transplantation is common.

Prognosis

• The prognosis is poor, with many patients having other extramedullary disease and poor survival rates. Most patients die within months of diagnosis. Even patients with aleukemic leukemia cutis or granulocytic sarcoma progress to systemic disease and should be treated systemically from the time of diagnosis.
• In a study of 26 patients with cutaneous infiltrates, Kaddu et al reported a median survival of 7.6 months for AML and 9.4 months for CLL, regardless of the treatment modality.
• A review of medical literature from 1965-2001 reported an overall survival rate of 6% at 2 years in patients with AML with leukemia cutis compared with 30% in those without leukemia cutis.

Patient Education

• Patients should notify their physician if any fevers or skin eruptions occur.
• For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education articles Leukemia and Skin Biopsy.

MISCELLANEOUS

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Medical/Legal Pitfalls

• The greatest medicolegal pitfall is in the case of aleukemic leukemia cutis.
• • If a biopsy is not performed promptly on the skin lesions, a delay in treatment results. If appropriate immunostaining is not performed and an incorrect diagnosis is made, treatment may be delayed.
  • One particularly difficult situation is the misdiagnosis of granulocytic sarcoma as lymphoma. If the patient is treated for lymphoma rather than leukemia, a great risk of disease progression and adverse effects of an unwarranted chemotherapeutic regimen exists.
  • Alternatively, misdiagnosis of a leukemic subtype could lead to incorrect therapy. If a patient has a known diagnosis of leukemia, misdiagnosis is less likely because the skin often shows the same markers as the bone marrow.
• Failure to perform a biopsy is a pitfall. A biopsy should be performed on a patient with an established diagnosis of leukemia with a suspected case of leukemia cutis because a concurrent different leukemia could be present or transformation of the original leukemia may have occurred. In either case, a skin biopsy may be the first and least invasive test to reveal this. If the biopsy is delayed, appropriate treatment is delayed.
• If leukemia cutis (extramedullary leukemia) is misdiagnosed as carcinoma or lymphoma and treated without leukemia-specific therapies, the prognosis is very poor.

MULTIMEDIA

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Media file 1:  Involvement of the face in a patient with acute myelogenous leukemia. Courtesy of Grant Anhalt, MD.
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Media file 2:  Red-brown papules can be seen in leukemia cutis. They are confluent in this patient. Courtesy of Nevena Damjanov, MD, and Elizabeth Prechtel.
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Media file 3:  Papules and nodules on the face of an African American patient with acute myelogenous leukemia (AML). Courtesy of Mona Mofid, MD.
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Media file 4:  A patient with typical plum-colored lesions seen in leukemia cutis. This patient had acute myelogenous leukemia. Courtesy of Grant Anhalt, MD.
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Media file 5:  This photograph shows linear areas, which are more violaceous in color, likely due to trauma to the area, such as excoriation, which results in hemorrhage into the skin. Frequent hemorrhage into the skin can make any inflammatory skin lesion appear more violaceous in patients with leukemia. Courtesy of Nevena Damjanov, MD, and Elizabeth Prechtel.
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Media file 6:  Low-power view of leukemia cutis acute myeloblastic leukemia (AML-M1). Note the perivascular and periadnexal infiltrate with relative epidermal sparing. Courtesy of Kim Hiatt, MD.
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Media file 7:  This is a higher power view of leukemia cutis acute myeloblastic leukemia (AML-M1). This photo illustrates a perivascular infiltrate of leukemic cells. The nuclei are round to oval with little cytoplasm. Courtesy of Kim Hiatt, MD.
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Media file 8:  Leukemia cutis of acute monocytic leukemia. Perivascular and periadnexal infiltration is also present, but the cell morphology is distinct. Many of the nuclei are folded or indented. The cytoplasm of the leukemic cells is gray-blue and more abundant than in the M1 subtype. Courtesy of Kim Hiatt, MD.
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Media file 9:  Low-power view of acute promyelocytic leukemia cutis with a perivascular and periadnexal but also interstitial infiltrate, with epidermal sparing but significant upper dermal edema, which could be confused with Sweet syndrome at a low-power view. Courtesy of Kim Hiatt, MD.
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Media file 10:  Acute promyelocytic leukemia cutis at high power. The round-to-indented nuclei with prominent cytoplasmic granules are evident. Courtesy of Kim Hiatt, MD.
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Media file 11:  Photo illustrates leukocyte esterase staining of the cytoplasm of the leukemic cells in acute promyelocytic leukemia. Courtesy of Kim Hiatt, MD.
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Media file 12:  Leukemia cutis at low power demonstrating a Grenz zone and intercalation of leukemic cells between collagen bundles. Courtesy of Keliegh Culpepper, MD.
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Media file 13:  A higher-power view of intercalation of leukemic cells between collagen bundles. Courtesy of Keliegh Culpepper, MD.
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REFERENCES

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

• Agis H, Weltermann A, Fonatsch C, et al. A comparative study on demographic, hematological, and cytogenetic findings and prognosis in acute myeloid leukemia with and without leukemia cutis. Ann Hematol. Feb 2002;81(2):90-5. [Medline].
• Appelbaum FR, Rowe JM, Radich J, Dick JE. Acute myeloid leukemia. Hematology (Am Soc Hematol Educ Program). 2001;62-86. [Medline].
• Auerbach M. Acute myeloid leukemia in patients more than 50 years of age: special considerations in diagnosis, treatment, and prognosis. Am J Med. Feb 1994;96(2):180-5. [Medline].
• Baer MR, Barcos M, Farrell H, et al. Acute myelogenous leukemia with leukemia cutis. Eighteen cases seenbetween 1969 and 1986. Cancer. Jun 1 1989;63(11):2192-200. [Medline].
• Bernstein L, Newton P, Ross RK. Epidemiology of hairy cell leukemia in Los Angeles County. Cancer Res. Jun 15 1990;50(12):3605-9. [Medline].
• Beynet D, Oro AE. Leukemia cutis presenting as a sister Mary Joseph nodule. Arch Dermatol. Sep 2004;140(9):1170-1. [Medline].
• Bonvalet D, Foldes C, Civatte J. Cutaneous manifestations in chronic lymphocytic leukemia. J Dermatol Surg Oncol. Apr 1984;10(4):278-82. [Medline].
• Braverman IM, ed. Skin Signs of Systemic Disease. 2^nd ed. 1981:179-96.
• Burns CA, Scott GA, Miller CC. Leukemia cutis at the site of trauma in a patient with Burkitt leukemia. Cutis. Jan 2005;75(1):54-6. [Medline].
• Cerroni L, Höfler G, Bäck B, et al. Specific cutaneous infiltrates of B-cell chronic lymphocytic leukemia (B-CLL) at sites typical for Borrelia burgdorferi infection. J Cutan Pathol. Mar 2002;29(3):142-7. [Medline].
• Chang HY, Wong KM, Bosenberg M, et al. Myelogenous leukemia cutis resembling stasis dermatitis. J Am Acad Dermatol. Jul 2003;49(1):128-9. [Medline].
• Chao SC, Lee JY, Tsao CJ. Leukemia cutis in acute lymphocytic leukemia masquerading as viralexanthem. J Dermatol. Apr 1999;26(4):216-9. [Medline].
• Connelly TJ, Kauh YC, Luscombe HA, Becker G. Leukemic macrocheilitis associated with hairy-cell leukemia and the Melkersson-Rosenthal syndrome. J Am Acad Dermatol. Feb 1986;14(2 Pt 2):353-8. [Medline].
• Daoud MS, Snow JL, Gibson LE, Daoud S. Aleukemic monocytic leukemia cutis. Mayo Clin Proc. Feb 1996;71(2):166-8. [Medline].
• Fadilah SA, Alawiyah AA, Amir MA, Cheong SK. Leukaemia cutis presenting as leonine facies. Med J Malaysia. Mar 2003;58(1):102-4. [Medline].
• Ferreira M, Caetano M, Amorim I. Leukemia cutis resembling a flare-up of psoriasis. Dermatol Online J. 2006;12(3):13. [Medline].
• Freiman A, Muhn CY, Trudel M, Billick RC. Leukemia cutis presenting with fingertip hypertrophy. J Cutan Med Surg. Jan-Feb 2003;7(1):57-60. [Medline].
• Giles FJ, Keating A, Goldstone AH, et al. Acute myeloid leukemia. Hematology (Am Soc Hematol Educ Program). 2002;73-110. [Medline].
• Heskel NS, White CR, Fryberger S, et al. Aleukemic leukemia cutis: juvenile chronic granulocytic leukemia presenting with figurate cutaneous lesions. J Am Acad Dermatol. Sep 1983;9(3):423-7. [Medline].
• High DA, Luscombe HA, Kauh YC. Leukemia cutis masquerading as chronic paronychia. Int J Dermatol. Nov 1985;24(9):595-7. [Medline].
• Ikeda T, Sakurane M, Uede K, Furukawa F. A case of symmetrical leukemia cutis on the eyelids complicated by B-cell chronic lymphocytic lymphoma. J Dermatol. Jul 2004;31(7):560-3. [Medline].
• Jones D, Dorfman DM, Barnhill RL. Leukemic vasculitis: a feature of leukemia cutis in some patients. Am J Clin Pathol. Jun 1997;107(6):637-42. [Medline].
• Kaddu S, Zenahlik P, Beham-Schmid C, et al. Specific cutaneous infiltrates in patients with myelogenous leukemia: aclinicopathologic study of 26 patients with assessment of diagnosticcriteria. J Am Acad Dermatol. Jun 1999;40(6 Pt 1):966-78. [Medline].
• Longacre TA, Smoller BR. Leukemia cutis. Analysis of 50 biopsy-proven cases with an emphasis onoccurrence in myelodysplastic syndromes. Am J Clin Pathol. Sep 1993;100(3):276-84. [Medline].
• Marcucci G, Byrd JC, Dai G, et al. Phase 1 and pharmacodynamic studies of G3139, a Bcl-2 antisenseoligonucleotide, in combination with chemotherapy in refractory orrelapsed acute leukemia. Blood. Jan 15 2003;101(2):425-32. [Medline].
• Miller MK, Strauchen JA, Nichols KT, Phelps RG. Concurrent chronic lymphocytic leukemia cutis and acute myelogenous leukemia cutis in a patient with untreated CLL. Am J Dermatopathol. Aug 2001;23(4):334-40. [Medline].
• Petrella T, Meijer CJ, Dalac S, et al. TCL1 and CLA expression in agranular CD4/CD56 hematodermic neoplasms (blastic NK-cell lymphomas) and leukemia cutis. Am J Clin Pathol. Aug 2004;122(2):307-13. [Medline].
• Piette WW. An approach to cutaneous changes caused by hematologic malignancies. Dermatol Clin. Jul 1989;7(3):467-79. [Medline].
• Poiesz BJ, Papsidero LD, Ehrlich G, et al. Prevalence of HTLV-I-associated T-cell lymphoma. Am J Hematol. Jan 2001;66(1):32-8. [Medline].
• Pranteda G, Gueli N, Innocenzi D. Skin vasculitis with direct vessel infiltration by leukaemic cells: a case report. Acta Derm Venereol. Jun-Jul 2001;81(3):215-6. [Medline].
• Ratnam KV, Khor CJ, Su WP. Leukemia cutis. Dermatol Clin. Apr 1994;12(2):419-31. [Medline].
• Ratnam KV, Su WP, Ziesmer SC, Li CY. Value of immunohistochemistry in the diagnosis of leukemia cutis: study of 54 cases using paraffin-section markers. J Cutan Pathol. Jun 1992;19(3):193-200. [Medline].
• Rekha A, Ravi A, Thanka J, Kuruvilla S. Chronic lower limb ulcer? No--chloroma!. Int J Low Extrem Wounds. Sep 2003;2(3):168-70. [Medline].
• Roboz GJ, Knovich MA, Bayer RL, et al. Efficacy and safety of gemtuzumab ozogamicin in patients with poor-prognosis acute myeloid leukemia. Leuk Lymphoma. Oct 2002;43(10):1951-5. [Medline].
• Sakalosky PE, Fenske N, Morgan MB. A case of acantholytic dermatosis and leukemia cutis: cause or effect?. Am J Dermatopathol. Jun 2002;24(3):257-9. [Medline].
• Schiffer CA, Sanel FT, Stechmiller BK, Wiernik PH. Functional and morphologic characteristics of the leukemic cells of a patient with acute monocytic leukemia: correlation with clinical features. Blood. Jul 1975;46(1):17-26. [Medline].
• Schneider LA, Weber L, Viardot A, et al. Cutaneous leukaemic infiltrations in a patient with previously undiagnosed myelodysplastic syndrome. Clin Exp Dermatol. Sep 2004;29(5):468-70. [Medline].
• Schwonzen M, Kuehn N, Vetten B, et al. Phenotyping of acute myelomonocytic (AMMOL) and monocyti