What cutaneous findings raise suspicion for a hematologic malignancy and what is the recommended diagnostic work‑up and management?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: February 18, 2026 • View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

Cutaneous Manifestations of Hematologic Malignancy

Direct Tumor Infiltration (Specific Lesions)

The most critical cutaneous finding requiring immediate workup is blastic plasmacytoid dendritic cell neoplasm (BPDCN), which presents as bruise-like nodules or tumors and carries a poor prognosis without prompt treatment. 1

BPDCN Presentation and Workup

  • Skin lesions appear as solitary or multiple red-brown to violaceous nodules and tumors, often with a bruise-like appearance 1

  • Approximately 90% of patients present with skin involvement, which may precede systemic disease 1

  • Mandatory workup includes:

    • Skin biopsy with immunohistochemistry and flow cytometry 1
    • Bone marrow biopsy and aspirate with cytogenetics 1
    • Complete blood count with differential and comprehensive metabolic panel 1
    • PET/CT scan if extramedullary disease or lymphadenopathy suspected 1
    • Lumbar puncture is highly recommended at diagnosis, as CNS involvement occurs in 9-26% of cases 1

  • Diagnostic criteria require expression of at least 4 of 6 antigens: CD123, CD4, CD56, TCL-1, CD2AP, and CD303/BDCA-2 1

  • TCF4/CD123 coexpression is highly sensitive and specific 1

  • Treatment priority is CD123-targeted therapy with tagraxofusp-ersz in appropriate candidates 1

Leukemia Cutis (AML)

  • Presents as papules, nodules, or plaques that may be skin-colored, red, or violaceous 1
  • Can occur at any extramedullary site including lymph nodes and spleen 1
  • Must be distinguished from BPDCN through experienced hematopathology review 1
  • Requires skin biopsy with morphology assessment, immunohistochemistry, flow cytometry, and cytogenetic analysis 1

Primary Cutaneous CD30+ Lymphoproliferative Disorders

  • Lymphomatoid papulosis (LYP): Recurrent self-healing papulonodular lesions that spontaneously regress within weeks 1
  • Primary cutaneous anaplastic large-cell lymphoma (PCALCL): Solitary or grouped nodular lesions without evidence of systemic disease 1

Workup for CD30+ disorders:

  • Complete blood count with differential, blood chemistry, and lactate dehydrogenase 1
  • For typical LYP with no systemic symptoms: radiologic staging is optional 1
  • For PCALCL: contrast-enhanced CT scan (chest, abdomen, pelvis) with or without PET is mandatory 1
  • Lymph node biopsy if nodes >1.5 cm detected 1
  • Bone marrow biopsy is optional in solitary PCALCL without radiologic evidence of extracutaneous disease 1

Mycosis Fungoides/Sézary Syndrome

  • Mycosis fungoides presents as patches and plaques, later developing tumors 1
  • Immunophenotype: CD3+, CD4+, CD45R0+, CD8– (rarely CD4–, CD8+) 1
  • Sézary syndrome presents with erythroderma, hyperkeratosis of palms/soles, lymphadenopathy, and alopecia 1
  • Requires skin biopsy, complete blood count, and assessment for circulating Sézary cells 1

Subcutaneous Panniculitis-Like T-Cell Lymphoma

  • Presents as solitary or multiple subcutaneous nodules to indurated plaque-like lesions 1
  • Immunophenotype: CD3+, CD4–, CD8+, cytotoxic proteins positive, typically TCRαβ+, CD56– 1

Paraneoplastic Manifestations (Non-Specific Lesions)

Sweet's Syndrome (Acute Febrile Neutrophilic Dermatosis)

  • Characterized by tender erythematous papules, nodules, or plaques with dermal infiltrate of mature neutrophils 2
  • Associated with acute myeloid leukemia and myelodysplastic syndromes 2
  • Responds to systemic corticosteroids but requires treatment of underlying malignancy for resolution 2

Pyoderma Gangrenosum

  • Presents as painful ulcers with violaceous undermined borders and purulent base 2, 3
  • Strongly associated with chronic myelomonocytic leukemia and other myeloid malignancies 3
  • Biopsy shows neutrophil infiltration with purulent inflammation 3
  • For patients with typical skin lesions and abnormal blood counts, investigate for hematologic malignancy 3
  • Treatment requires hormones and infection control, but prognosis depends on underlying malignancy control 3

Vesiculobullous Conditions

  • Paraneoplastic pemphigus: erythema multiforme-like lesions associated with lymphoproliferative disorders 2
  • Pemphigus vulgaris: large flaccid bullae 2
  • Pemphigus foliaceus: superficial crusted erosions 2
  • Requires systemic corticosteroids but resolution depends on malignancy eradication 2

Eosinophilic Dermatosis of Hematologic Malignancy

  • Presents as pruritic, erythematous, papular, vesicular, or urticarial eruptions 4
  • Strongly associated with chronic lymphocytic leukemia 4
  • Histopathology shows prominent eosinophil infiltration with possible flame figures 4
  • This term is preferred over "eosinophilic cellulitis" when associated with hematoproliferative disease 4

Vascular Manifestations

  • Vasculitis: palpable purpura or ulcerations 2
  • Erythromelalgia: burning pain with erythema of extremities 2

Critical Diagnostic Pitfalls

Common mistake: Dismissing atypical psoriasis-like plaques in groin/buttock areas as benign psoriasis 1

  • Development of atypical psoriasis plaques in these locations should raise suspicion for cutaneous T-cell lymphoma 1
  • Requires complete lymph node examination and skin biopsy 1

Common mistake: Assuming all self-healing papulonodular lesions are benign

  • Must distinguish LYP from other CD30+ disorders through proper immunophenotyping 1
  • LYP patients may concurrently develop mycosis fungoides 1

Common mistake: Inadequate biopsy technique

  • Cutaneous lesions may not yield sufficient cells for flow cytometry if biopsy is too superficial 1
  • Full-thickness excisional or adequate incisional biopsy (≥4mm punch) is mandatory 1

Management Algorithm

Step 1: Identify lesion morphology

  • Bruise-like nodules → suspect BPDCN
  • Self-healing papulonodules → suspect LYP
  • Patches/plaques → suspect mycosis fungoides
  • Painful ulcers with undermined borders → suspect pyoderma gangrenosum
  • Tender erythematous plaques with fever → suspect Sweet's syndrome

Step 2: Obtain proper tissue diagnosis

  • Full-thickness biopsy with immunohistochemistry and flow cytometry 1
  • Send for cytogenetic analysis if infiltrative process suspected 1

Step 3: Stage appropriately based on diagnosis

  • BPDCN: bone marrow biopsy, PET/CT, lumbar puncture 1
  • PCALCL: contrast-enhanced CT chest/abdomen/pelvis 1
  • LYP with typical presentation: staging optional if no systemic symptoms 1

Step 4: Initiate treatment

  • BPDCN: tagraxofusp-ersz (CD123-targeted therapy) 1
  • Paraneoplastic conditions: treat underlying malignancy for definitive resolution 2, 3

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Related Questions

I have a subcutaneous, fluctuating, tender, bruised‑purple swelling about the size of half a baseball above my elbow that appeared after a venipuncture, worsens throughout the day, resolves by morning, has an itchy erythematous rim, and is not associated with fever, warmth, paresthesia, or limited motion; what is the likely diagnosis and appropriate management?
Is it safe to take famotidine before Vyvanse (lisdexamfetamine) without adjusting doses?
Is scalp micropigmentation safe after a hair transplant, and how long should an adult patient wait (e.g., 12‑18 months) if there is no scalp infection, uncontrolled dermatologic disease, pigment allergy, or bleeding disorder?
What empiric antibiotic regimen should be started for an adult with sepsis secondary to gangrene, including coverage for MRSA (Methicillin‑resistant Staphylococcus aureus), Pseudomonas, anaerobes, and considerations for beta‑lactam allergy?
What are the standard adult antibiotic regimens for infective endocarditis, including organism‑specific recommendations for native‑valve and prosthetic‑valve infections?
In a patient without risk factors for multidrug‑resistant organisms (not in ICU, no recent broad‑spectrum antibiotic exposure, no colonization with Pseudomonas aeruginosa or MRSA), does levofloxacin provide adequate coverage for hospital‑acquired pneumonia?
In a male patient with clinical appendicitis (abdominal rigidity and tenderness) whose appendix appears normal intraoperatively, should the appendix be removed and the abdomen closed?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.

Ask Question