Transcript C-50_Fletcherlx - Advocate Health Care

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
Introduction
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 Description
Differential Diagnosis
Immunocompetent
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
Patient A: 14 year old male with known acute myeloid leukemia,
Intervention
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.
Immunocompromised
Excisional biopsies were performed on lesions from both patients and
sent for histopathology and immunophenotyping.
Histopathology
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
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
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: + Eczema
Immunizations: UTD. Medications: None
Social 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 restrictions
PE: 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
Subcutaneous infiltrate of polymorphic
mononuclear cells with wrinkled nuclei
(low and high power)
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
Results
Biopsy Results: Mononuclear infiltrate, consistent with acute
monoblastic leukemia, (Subtype M5) involving the dermis and
subcutaneous tissue .
Leukemia Cutis
Conclusion
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
• 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.
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.
Implications
•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.
References
• 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 .
Acknowledgements
To all of the physicians, nursing and staff who cared for our patients
during their treatment at Hope Children’s Hospital.