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Skin melanocytic tumor

Melanoma

Superficial spreading melanoma (low CSD melanoma)

Author: Bethany R. Rohr, M.D.

Deputy Editor-in-Chief: Jonathan D. Ho, M.B.B.S., D.Sc.

Last author update: 4 October 2023

Last staff update: 26 February 2024

Copyright: 2021-2024, PathologyOutlines.com, Inc.

PubMed Search: Superficial spreading melanoma

Table of Contents

Cite this page: Rohr BR. Superficial spreading melanoma (low CSD melanoma). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/skintumormelanocyticsuperficialspreadingmelanomalowCSD.html. Accessed December 28th, 2024.

Definition / general

Superficial spreading melanoma (SSM) is the most common subtype of melanoma in the Western world (Arch Pathol Lab Med 2020;144:500)

Essential features

Develops on sun exposed sites with low cumulative sun damage (CSD) (Arch Pathol Lab Med 2020;144:500)
Has a radial growth phase (Arch Pathol Lab Med 2020;144:500)
Most common mutation in superficial spreading melanoma is BRAF^V600E (Arch Pathol Lab Med 2020;144:500)

Terminology

Pagetoid melanoma (Arch Pathol Lab Med 2020;144:500)

ICD coding

ICD-10: C43.9 - malignant melanoma of skin, unspecified
ICD-11
- 2C30.0 - superficial spreading melanoma, primary
- 2C30.Y - other specified melanoma of skin
- 2C30.Z - melanoma of skin, unspecified

Epidemiology

Superficial spreading melanoma accounts for up to 56% of cutaneous melanomas (Br J Dermatol 2021;185:700)
Low cumulative sun damage (Arch Pathol Lab Med 2020;144:500)
- Intermittent sun exposure throughout childhood
- Tanning bed use
Increased total number of melanocytic nevi (Arch Pathol Lab Med 2020;144:500)
Dysplastic nevi (Arch Pathol Lab Med 2020;144:500)
Increased size of nevi (Arch Pathol Lab Med 2020;144:500)

Sites

Back in men (Arch Pathol Lab Med 2020;144:500)
Legs, calves in women (Arch Pathol Lab Med 2020;144:500)

Pathophysiology

Mutation patterns overlap with other melanoma subtypes
Low CSD melanoma (Arch Pathol Lab Med 2020;144:500)
Mutations (Arch Pathol Lab Med 2020;144:500)
- BRAF most common
  - V600E most common amongst BRAF
- NRAS
- TERT
- Biallelic inactivation of CDKN2A
- PTEN, TP53 in advanced primary melanomas

Etiology

Low cumulative sun damage (Arch Pathol Lab Med 2020;144:500)
- Intermittent sun exposure and sunburns

Clinical features

Irregular red, brown or black macule, patch, papule or plaque (Arch Pathol Lab Med 2020;144:500)
ABCDE: asymmetry, border irregularity, color variation, diameter > 6 mm, other evolution history

Diagnosis

Excisional biopsy
Histopathologic diagnosis is gold standard
Sentinel lymph node biopsy (SLNB)
- For primary tumors with Breslow depth of 0.8 mm or deeper
  - Consider SLNB if < 0.8 mm with ulceration
- Breslow depth: measured from the top of the granular layer or base of ulceration to the deepest invasive melanoma cell
References: Ital J Dermatol Venerol 2021;156:300, NCCN: NCCN Guidelines - Melanoma: Cutaneous [Accessed 3 October 2023]

Prognostic factors

Adverse prognosis indicators (Ital J Dermatol Venerol 2021;156:300)
- Thicker (Breslow) depth: most important
- Presence of ulceration
- Dermal mitoses
- Deeper anatomic (Clark) level of invasion (I-V)
- Presence of lymphovascular invasion
- Presence of neurotropism
  - Increased risk of local recurrence
- Presence of sentinel lymph node biopsy (SLNB)
- Positive excision margins
  - Report proximity of melanoma in situ or invasive melanoma to excision margins when able

Case reports

32 year old man with primary superficial spreading melanoma recurring with desmoplastic melanoma features (Virchows Arch 2022;480:945)
47 year old woman with superficial spreading melanoma developing within a nevus spilus (J Osteopath Med 2023;123:223)
78 year old man with a history of superficial spreading melanoma developing a malignant peripheral nerve sheath tumor (World J Clin Cases 2021;9:6457)

Treatment

Treatment includes excision with or without sentinel lymph node biopsy; additional treatment based on stage (NIH: Melanoma Treatment (PDQ®) - Health Professional Version [Accessed 7 July 2023], NCCN: NCCN Guidelines - Melanoma: Cutaneous [Accessed 3 October 2023], American Cancer Society: Immunotherapy for Melanoma Skin Cancer [Accessed 3 October 2023])
- Wide local excision 1 - 2 cm
- SLNB for primary tumors with Breslow depth of 0.8 mm or deeper
  - Consider SLNB if < 0.8 mm with ulceration
  - No clinical or radiographic evidence of nodal disease
- Targeted or immunotherapy / checkpoint inhibitors
  - Targeted therapies include BRAF and MEK inhibitors
  - Immune checkpoint inhibitors include PD1, PDL1, CTLA4 and LAG3 inhibitors
- Talimogene laherparepvec (T-VEC) injections
- Interleukin 2
- Chemotherapy
- Radiation therapy
- Regular skin examination with a dermatologist

Clinical images

Images hosted on other servers:

Irregularly pigmented plaques

Dermoscopy

Microscopic (histologic) description

Radial growth phase with or without vertical growth phase (Arch Pathol Lab Med 2020;144:500)
- Large epithelioid melanocytes
- Prominent junctional and intraepidermal component
- Irregular and enlarged nests of melanocytes along dermal - epidermal junction
- Junctional melanocyte confluence
- Dermal component is composed of similar appearing melanocytes that fail to mature and disperse with descent; dermal mitoses are noted
- Pagetoid scatter
  - Presence of melanocytes above the basal layer
- If invasive
  - Failure of dermal melanocytes to mature (i.e., become smaller) and disperse (i.e., smaller nests, single unit melanocytes) with descent into the dermis
  - With or without dermal mitotic figures
With or without melanin pigmentation
Absent to moderate underlying solar elastosis
Lacks severe solar elastosis
Precursor or associated melanocytic nevus may be present (Arch Dermatol 2003;139:1620)
- Most frequent melanoma subtype to arise with a nevus
Pathologic stage classification AJCC guidelines, eighth edition (2018) (Ital J Dermatol Venerol 2021;156:300)
- Tumor (Breslow) depth is the strongest predictor of clinical outcome, used for staging
  - Measure vertically from the top of granular layer of the epidermis to the deepest invasive melanoma cells
  - If ulcerated, measure from base of ulcer
  - Round to nearest 0.1 mm using ocular micrometer
  - Avoid measuring vascular invasion, microsatellites, involvement of skin appendages

Microscopic (histologic) images

Contributed by Bethany R. Rohr, M.D.

Epithelioid melanocytes

Pagetoid melanocytes

Poorly nested melanocytes

Atypical melanocytes

SOX10 immunostain

HMB45 immunostain

Positive stains

SOX10 (nuclear)
MART1, also known as MelanA (cytoplasmic)
PRAME
HMB45
S100
MITF
Tyrosinase
BRAF variable
Reference: Semin Diagn Pathol 2022;39:239

Negative stains

Loss of melanocytic markers is possible (Dermatopathology (Basel) 2021;8:359)
Keratin immunostains
- CK, AE1 / AE3, OSCAR, CAM5.2
- Rare aberrant expression in melanoma (Dermatopathology (Basel) 2021;8:359)
Neuroendocrine markers
- Neurofilament, glial fibrillary acidic protein, synaptophysin, chromogranin, CD56
- Rare aberrant expression in melanoma (Dermatopathology (Basel) 2021;8:359)
Muscle specific markers
- SMA, desmin, myoglobin, calponin
- Rare positivity, particularly in melanoma with rhabdomyosarcomatous differentiation
Macrophage markers
- CD68, CD163
- Rare aberrant expression in melanoma (Dermatopathology (Basel) 2021;8:359)
Vascular markers
- CD31, CD34
- Rare aberrant expression in melanoma (Dermatopathology (Basel) 2021;8:359)
Hematopoietic markers
- CD4, CD20
- Rare aberrant expression in melanoma (Dermatopathology (Basel) 2021;8:359)
Miscellaneous
- FLI1, GATA3, CEA, calretinin, PAX8, PAX2
- Rare aberrant expression in melanoma (Dermatopathology (Basel) 2021;8:359)

Videos

Superficial spreading melanoma
by Dr. Jerad Gardner

Sample pathology report

Skin, biopsy:
- Invasive malignant melanoma, superficial spreading subtype, extending to a Breslow depth of ## (see comment)
- Comment: The sections reveal a severely atypical compound melanocytic proliferation composed of atypical epithelioid melanocytes. The melanocytes are poorly nested along the dermal - epidermal junction with confluence and pagetoid scatter. The dermal component is composed of similar appearing melanocytes that fail to mature and disperse with descent. Dermal mitoses are noted.

Differential diagnosis

Lentigo maligna melanoma:
- High cumulative sun damage
  - Significant dermal solar elastosis
- Pagetoid scatter is less prominent
- Radial growth phase
- More common on chronically sun exposed sites of elderly, light skinned adults
Acral lentiginous melanoma:
- Acral sites
- Noncumulative sun damage related
Nevoid melanoma (Ital J Dermatol Venerol 2021;156:300):
- Resembles intradermal nevus, 2 types
- Papillomatous type
  - NRAS mutation most common
  - Head, neck, limbs
  - Puffy shirt appearance: scanning magnification shows dense cellular aggregates surrounded by bent elongated rete ridges lined up side by side
- Maturing nevoid type: limbs, trunk
  - Heterogeneous mutations: BRAF, NRAS
Nodular melanoma:
- Low or high cumulative sun damage
- No radial growth phase
Cutaneous involvement of metastatic malignant melanoma:
- History of prior locoregional invasive melanoma
- Features that favor metastases (Arch Pathol Lab Med 2020;144:500)
  - Tumor size of < 2 mm
  - Absence of tumor infiltrating lymphocytes and plasma cells
  - Monomorphism
  - Involvement of adnexal epithelium

Additional references

Mod Pathol 2018;31:24

Board review style question #1

Superficial spreading melanoma is most commonly associated with which mutation?

BRAF
NRAS
PTEN
TERT
TP53

Board review style answer #1

A. BRAF is the most commonly mutated driver oncogene in low cumulative sun damage melanoma. The most common mutation is the p. V600E. Answers B - E are incorrect because NRAS, TERT, PTEN and TP53 are less commonly mutated in superficial spreading melanoma.

Comment Here

Reference: Superficial spreading melanoma (low CSD melanoma)

Board review style question #2

From which of the following pathways does superficial spreading melanoma develop?

Both high and low cumulative sun damage
High cumulative sun damage
Low cumulative sun damage
No association with cumulative sun damage

Board review style answer #2

C. Low cumulative sun damage. Superficial spreading melanoma arises on sun exposed skin sites with little underlying solar elastosis. Answer B is incorrect since high cumulative sun damage is associated with lentigo maligna melanoma. Answer D is incorrect since superficial melanoma is associated with low cumulative sun damage. Answer A is incorrect because nodular melanoma may be associated with both high and low cumulative sun damage.

Comment Here

Reference: Superficial spreading melanoma (low CSD melanoma)

Board review style question #3

Which subtype of melanoma is most likely to arise in association with a precursor melanocytic nevus?

Acral lentiginous
Lentigo maligna
Nodular
Primary dermal
Superficial spreading

Board review style answer #3

E. Superficial spreading melanoma is the most frequent histologic subtype of melanoma to be found arising in association with a melanocytic nevus. Other predictors of melanoma arising in association with a nevus include younger age and truncal location (Arch Dermatol 2003;139:1620). Answers A - D are incorrect because these other melanoma subtypes are less commonly documented to arise in association with a precursor melanocytic nevus.

Comment Here

Reference: Superficial spreading melanoma (low CSD melanoma)

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