Differentials

Basal cell carcinoma (BCC)

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

  • Slow growing.

  • Presents as pearly papules or plaques with rolled borders, telangiectasias, and ulceration when tumors become larger.

INVESTIGATIONS

  • Dermoscopy: crisp and well-defined arborizing vessels, spoke wheel-like pigment clods and maple leaf structures, milky-white background.[57]

  • Histopathology: hematoxylin and eosin (H&E) features consistent with BCC include basaloid tumor with peripheral palisading, clefting, and distinctive stroma.

Basal cell carcinoma

Squamous cell carcinoma (SCC) of the skin

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

  • Typically grows more slowly, although keratoacanthoma is a fast-growing variant.

  • Hyperkeratotic scale is more common in cutaneous SCCs compared with MCC.[58][59]​​​

INVESTIGATIONS

  • Dermoscopy: white circles and glomeruloid vessels.

  • Histopathology: H&E features consistent with SCC include atypical squamous cells infiltrating into dermis.

Squamous cell carcinoma of the skin

Amelanotic/hypomelanotic melanoma

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

  • Younger age of presentation compared with MCC. More than two-thirds of melanoma cases in the California Cancer Registry over a 15-year period occurred in people younger than 70 years, with a median age of 57 years.[60]

  • Occurs more frequently on the trunk than MCC.[60]

INVESTIGATIONS

  • Dermoscopy: hypomelanotic melanoma can show pigmented structures or blue-gray veil.[61]

  • Histopathology: skin biopsy with H&E features diagnostic of melanoma (e.g., severely cytologically atypical melanocytes, with an asymmetric growth pattern, Pagetoid spread of melanocytes, and confluent growth with a loss of the normal nested pattern). Immunohistochemical markers for melanocytic lesions include S100, HMB45, Sox10, and MelanA.

Melanoma

Cutaneous metastasis of small cell lung carcinoma (SCLC) or other pulmonary neuroendocrine tumor

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

  • Favors the scalp or trunk.[62][63]​​​

  • Typically accompanied by respiratory symptoms.

INVESTIGATIONS

  • Immunohistochemistry: SCLC is generally positive for TTF-1 and CK7, and negative for CK20.[43]

  • Imaging: mass or adenopathy on chest CT.[3]

Small cell lung cancer

Cutaneous metastasis of other nonpulmonary visceral neuroendocrine tumor (gastrointestinal, mammary, urothelial/renal, pancreatic)

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

  • In one case series, metastatic neuroendocrine tumors were characterized by a single well-defined nodular neoplasm in the dermis and subcutis.[63]

  • Another study of 14 patients showed the most common locations for metastasis were the head and neck (n=7), chest, and breast (n=4).[64]

INVESTIGATIONS

  • Broad immunohistochemistry panel including CK20, TTF-1, neurofilament (NF), CK7, CDX2, GATA-3, SATB2, and progesterone receptors.[64][65]​​​ Gastrointestinal: positive for CDX2, negative for CK20, TTF-1, NF. Appendix and rectum: positive for SATB2, negative for TTF-1. Breast/mammary and urothelium: positive for GATA 3. Pancreatic: positive for progesterone receptor (PR), negative for SATB2.

  • Imaging: complete radiologic imaging with clinical correlation to identify a noncutaneous primary neuroendocrine tumor.[64]

Epidermal inclusion cyst

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

  • Fluctuant nodules that can be found on the head, neck, and upper torso, often with a central opening (punctum).[66][67]​​​

  • Inflamed cysts are often painful.

INVESTIGATIONS

  • Often a clinical diagnosis, based on history and physical exam.

  • Histopathology: cystic structure with a cell wall that has a granular layer and is filled with keratinaceous material.[67]

Pyogenic granuloma

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

  • Raised (exophytic), red papule that is friable, with a collarette of scale that bleeds easily.

  • Commonly on sites of trauma, such as the face, hands, or mucous membranes.[68]

INVESTIGATIONS

  • Often a clinical diagnosis.

  • Dermoscopy: milky-red areas, but often with a base with a collarette of scale.[68]

  • Histopathology: a lobular lesion with many capillaries made up of bland endothelial cells.[68]

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