New Frontiers in Pathology: An Update for Practicing Pathologists Case 6

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New Frontiers in Pathology An Update for
Practicing PathologistsCase 6

• Lori Lowe, M.D.
• University of Michigan
• Professor of Pathology Dermatology
• Director, Dermatopathology Service

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Case 6
Case History

• 39-year old male
• Asymptomatic pink nodule on right nose
• History of antecedent trauma to the site
• Clinical impression hypertrophic scar vs. cyst
  vs. adnexal tumor

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S100
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Melan-A
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CD 34
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Case 6
Diagnosis Desmoplastic Melanoma
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Desmoplastic Melanoma

• Clinical Features
• Rare fibrosing variant of melanoma
• Head and neck
• Middle-aged to elderly patients
• 40-50 cases associated with lentigo maligna
• Firm nodule or plaque
• Clinical resemblance to hypertrophic scar,
  dermatofibroma
• Early detection uncommon

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Lentigo Maligna (Melanoma in situ)
40-50 of Desmoplastic Melanoma arises in
association with lentigo maligna
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Desmoplastic Melanoma
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Desmoplastic Melanoma
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Desmoplastic Melanoma
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Desmoplastic Melanoma

• Histologic Features
• Haphazardly arranged fascicles of fusiform to
  spindled cells in dermis
• Infiltrative growth pattern
• Variable cellular density, cytologic atypia, and
  stromal desmoplasia
• Hyperchromatic spindled cells with pleomorphism
• Subtle, wavy spindle cell proliferation with low
  grade atypia, simulating Schwann cells or
  fibroblasts
• Neurotropism
• Pockets of lymphocytic inflammation
• Atypical junctional melanocytic proliferation in
  45 cases
• S100 positive, Melan-A HMB-45 often negative

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Demoplastic Melanoma, re-excision specimen
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Expansion of subcutaneous septae Infiltration of
skeletal muscle
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Diffuse spindle cell proliferation
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Spindle cells Collagenous stroma Myxoid background
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Paucicellular area Myxoid stroma
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Cellular area Desmoplastic stroma
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Variable pleomorphism
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Pocket of lymphocytes
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Pocket of lymphocytes
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Neurotropism
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Desmoplastic Melanoma
Atypical Junctional Melanocytic Hyperplasia
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Desmoplastic Melanoma
Important Points

• Distinct from conventional melanoma
• Decreased melanocyte differentiation gene
  expression by gene expression profiling
• BRAF mutations uncommon
• Local recurrences due to subclinical extension
• Decreased tendency for regional metastases with
  pure lesions (paucicellular and stromal
  desmoplasia)
• Overall better prognosis than other histologic
  subtypes

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Desmoplastic Melanoma

• Investigators Tumor Thickness (mm)
  SLNs/No. of Pts
• UCSF Mean 3.9
  1/29
• Mayo Clinic Mean 6.5
  0/16
• MSKCC Mean 2.2
  0/24
• U of M Mean 6.1
  4/33

Busam KJ, Cutaneous desmoplastic melanoma. Adv
Anat Pathol, 20051292-102
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Desmoplastic Melanoma
Most Common Diagnostic Errors

• Hypertrophic scar
• Dermatofibroma
• Neurofibroma/atypical neurofibroma
• Dermatofibrosarcoma protuberans
• Other malignant spindle cell neoplasms (i.e.
  atypical fibroxanthoma, leiomyosarcoma, etc.)
• Malignant peripheral nerve sheath tumor
• Missed completely!

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Desmoplastic Melanoma

• Early lesions particularly challenging
• Prone to misdiagnosis, especially with partial
  biopsies
• Beware the atypical neurofibroma on sun-damaged
  skin
• Wolf in sheeps clothes!

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Early Desmoplastic Melanoma
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S100
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Early desmoplastic melanoma misdiagnosed
as neurofibroma!
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Early Desmoplastic Melanoma
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S 100
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Early desmoplastic melanoma misdiagnosed
as actinic keratosis!
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Early Desmoplastic Melanoma
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Early invasive desmoplastic melanoma misdiagnosed
as atypical junctional melanocytic
proliferation.
Atypical junctional melanocytic proliferation
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Malignant Peripheral Nerve Sheath Tumor
Desmoplastic Melanoma
vs.

• Head and neck
• Located in dermis
• No history of NF1
• Not associated with nerve
• Diffuse S100 positivity

• Off of head and neck
• Located in deep soft tissues
• History of NF1
• Associated with nerve trunk
• Focal S100 positivty

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Desmoplastic Melanoma
Key Points

• Maintain high index of suspicion
• Can be subtle in its histologic presentation
• Helpful features include

Spindle cell proliferation Variable
pleomorphism Pockets of lymphocytes
Atypical junctional melanocytic proliferation (if
lucky) S100 positivity
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Enjoy fall in Ann Arbor!