• Cutaneous manifestations of systemic diseases are common and should be evaluated thoroughly.

• Leukemia cutis is an uncommon presentation of AML.• Leukemic skin lesions can present with different

expression at different points of disease.• 90% of patients with leukemia cutis have involvement of

other extramedullary sites and are often burdened with high leukemic tumor load.

• Treatment is aimed at eradicating the systemic disease. • Complete remission is achievable, but leukemia cutis

implicates a poor prognosis.• >80% of patients dying within 1 year of diagnosis, as

demonstrated by our patient cases.

Leukemia Cutis: A Diagnostic Symptom Seen at Presentation and Relapse in Acute Myeloid

Leukemia Corrie Fletcher DO, Emily Mueller MD, Sharad Salvi MD, Ammary Hayani, MD, Rebecca McFall, MD Jason Canner DO

Department of Pediatrics, Advocate Hope Children’s Hospital

Leukemia Cutis: A Diagnostic Symptom Seen at Presentation and Relapse in Acute Myeloid

Leukemia Corrie Fletcher DO, Emily Mueller MD, Sharad Salvi MD, Ammary Hayani, MD, Rebecca McFall, MD Jason Canner DO

Department of Pediatrics, Advocate Hope Children’s Hospital

Leukemia cutis is a cutaneous infiltration by neoplastic leukocytes resulting in clinically identifiable skin lesions. It occurs with acute myeloid leukemia (AML) and chronic myeloproliferative diseases, although occurring in only 10-15% of patients with AML.

We describe a unique set of cases where two adolescent males with AML present with leukemia cutis: one presenting with skin lesions indicating relapse and the seconds initial presentation demonstrating cutaneous findings.

Patient A: Repeat bone marrow biopsy confirmed AML relapse, as demonstrated with the dermatologic infiltration of leukemic cells. Patient restarted on chemotherapy per Children’s Oncology Group protocol, using high dose chemotherapy followed by stem cell transplant.

Early recurrence (<18 months) with presence of leukemia cutis is associated with worse prognosis.

Patient B Bone marrow aspirate/biopsy confirmed M4 AML. Pt started on induction chemotherapy, with cytarabine, etoposide and daunorubicin. Lumbar puncture confirmed CSF infiltration, and was additionally started on triple intrathecal chemotherapy.

Both patients ultimately succumbed to their disease and passed away within 10 months of diagnosis.

Patient A Right arm; punch skin biopsy Patchy mononuclear infiltrate of deep adenexal structures with confluent infiltrate in subcutaneous adipose tissue

Patient A: Skin nodules found on patient’s arms and shin

Subcutaneous infiltrate of polymorphic mononuclear cells with

wrinkled nuclei (low and high power)

Introduction Conclusion

References

Differential DiagnosisBiopsy Results: Mononuclear infiltrate, consistent with acute monoblastic leukemia, (Subtype M5) involving the dermis and subcutaneous tissue .

Results

Patient Description

Excisional biopsies were performed on lesions from both patients and sent for histopathology and immunophenotyping.

Intervention

Acute monoblastic leukemia, M5 involving dermis and subcutaneous tissue of skin

Karyotyping of skin infiltrate showed rearrangement in the 11q23 region in 173 of 200 cells

L: CD45 (LCA) R: Leder stain

Patient B: 15 year old male presented with 4 month history of URI symptoms, fever and rash.

Medical History: Pt initially seen by dermatology after development of a rash 4 months earlier. CBC was unremarkable. Skin biopsy was diagnostic for granuloma annulare, and prednisone was started. After 3 months, rash persisted with new onset gingival hyperplasia. Repeat CBC showed neutropenia and thrombocytopenia and repeat biopsy was completed.PMHx: + EczemaImmunizations: UTD. Medications: NoneSocial hx: Pt lives at home with parents and 3 younger siblings. No pets. Pt was born in England and is currently in 10th grade. He denies any etoh, tobacco, or drug use. He follows Halal dietary restrictionsPE: Skin—Raised, hyperpigmented nodules diffusely covering UE and LE, back and torso. Variable sizes between 1-2cm diameter. Nodules with defined borders and blanching. HEENT—gingival hyperplasia upper >lower LN—Post-auricular, anterior and posterior cervical, and submental lymphadenopathy. No supraclavicular or axillary LAD

Patient A: 14 year old male with known acute myeloid leukemia, type M5, presenting with skin lesions following completion of therapy.

Medical History: Pt presented 9 months prior to event with fatigue and shortness of breath. Initial CBC revealed WBC 174,000 and 85% blasts. Bone marrow was consistent with AML, M5. Pt underwent induction chemotherapy with cytarabine, daunorubicin, etoposide, and then intensification therapy eventually achieving remission. Hospital course was complicated by multiple episodes of febrile neutropenia. Following the completion of all chemotherapy, pt was noted to have several new skin lesions.PMHx: Mild asthma. No previous hospitalizations or surgeries.Sochx: Denies etoh, tobacco, or drug use.PE: Four to five 1-2 cm nodules, diffusely on R arm, L arm, L shin and scalp. Nodules are erythematous/violaceous, firm, non-tender and non-mobile. No surrounding erythema, edema or warmth.

Diagnosis based on morphologic pattern of skin infiltration & cytology

• Myeloid (Granulocytic) sarcoma• Nodular with perivascular-periadnexal distribution (interstitial + diffuse)• Predominately myeloblasts and granulocytic precursors

• Myeloid (Monoblastic) sarcoma• Infiltrate similar to above• Subcutaneous tissue involvement• Blastic chromatin and promonocytic features

• Large cleaved nuclei, small nucleoli and amphophilic cytoplasm• Histological Stains:

• (+)Myeloperoxidase (MPO) -neoplasms of granulocytic lineage• (+)Lysozyme - Marker for granulocytes, monocytes, macrophages

• Negative in lymphoid neoplasms• (+)CD 56 - neural cell adhesion molecule expressed by NK cells and subset of • T cells and monocytes

• Expression well recognized in AML, especially monocytic

Histopathology

Leukemia Cutis

• What is it?– Cutaneous infiltration by neoplastic leukocytes (myeloid or

lymphoid), resulting in clinically identifiable cutaneous lesions.• Where can it be found?

– Acute Myelogenous Leukemia– Chronic myeloproliferative disease

• Chronic Myelogenous Leukemia• Myelodysplastic syndromes• Myeloproliferative/lymphoproliferative diseases

– Within chronic disease pathology - associated with transformation into a blastic phase and suggests disease progression.

• Who gets it?– No consistent demographic or clinical differences.– Appears to be increased incidence among children.– Increased incidence with Chromosome 8 abnormalities.– Occurs in 10-15% of patients with AML.

• Up to 50% in M4, M5.• 1% in precursor B- or T-cell leukemia/lymphoma.

–25-30% of children with congenital leukemia.• Most pediatric patients have high leukemic tumor load and

hepatosplenomegaly.• What does it look like?

– Single or multiple lesions.– Described as violaceous, red-brown or hemorrhagic papules,

nodules and/or plaques of varying sizes:– Most common - erythematous papules.

– Legs most common, followed by arms, back, chest, scalp, face.• How is it treated?

– L. Cutis is a local manifestation of a systemic disease; therefore, treatment aimed at eradicating leukemia.

• What is the prognosis?– As many as 90% with leukemia cutis have involvement of

other extramedullary sites:• Meninges most frequent (40% of cases).

– Leukemia cutis in AML or CML:• Disease will follow an aggressive course and survival is

short.– Su, et al estimated that 88% of patients died within one year of

diagnosis.

• Kleigman et al. Nelson’s Textbook of Pediatrics 18th Edition. “Chapter 495, The Leukemias.” 2120-2122.

• Cho-Vega J, et al. “Leukemia cutis.” American Journal of Clinical Pathology. 2008;129:130-142.• Goldman et al. Cecil Medicine, 23rd ed. “Chapter 466: Urticaria, Drug Hypersensitivity Rashes,

Nodules and Tumors, and Atrophic Diseases.” www.mdconsult.com• Shipley J, et al. “Acute myeologenous leukemia.” Experimental Hematology 2009;37:649-658.• Curesearch: Children’s Oncology Group. “AAML0531: A Phase III Randomized Trial of

Gentuzumab Ozogamicin Combined with Conventional Chemotherapy for De Novo Acute Myeloid Leukemia (AML) in Children, Adolescents, and Young Adults.” www.childrensonologygroup.org

• Pearce and Sills. “Consultation with the Specialist: Childhood Leukemia” Pediatrics in Review. 2005;26:96-104.

• Segel and Halterman. “Neutropenia in Pediatric Practice.” Pediatrics in Review. 2008;29:12-24 .

AcknowledgementsTo all of the physicians, nursing and staff who cared for our patients during their treatment at Hope Children’s Hospital.

Implications

Immunocompetent Immunocompromised

Dermatologic: Granuloma annulare Sweet Syndrome

Rheumatologic/Autoimmune: - Sarcoidosis

Pyoderma gangrenosum

Primary malignancy: - Basal cell carcinoma - Melanoma

Infectious: - Septic emboli - Disseminated candidal infection - Disseminated herpes zoster - Severe/atypical herpes simplex

Petechiae Lymphoclastic vasculitis

Leukemia Lymphoma