Simulators of squamous cell carcinoma of the skin: diagnostic challenges on small biopsies and clinicopathological correlation

Abstract

Squamous cell carcinoma (SCC) is a common and important primary cutaneous malignancy. On skin biopsies, SCC is characterized by significant squamous cell atypia, abnormal keratinization, and invasive features. Diagnostic challenges may occasionally arise, especially in the setting of small punch biopsies or superficial shave biopsies, where only part of the lesion may be assessable by the pathologist. Benign mimics of SCC include pseudoepitheliomatous hyperplasia, eccrine squamous syringometaplasia, inverted follicular keratosis, and keratoacanthoma, while malignant mimics of SCC include basal cell carcinoma, melanoma, and metastatic carcinoma. The careful application of time-honored diagnostic criteria, close clinicopathological correlation and a selective request for a further, deeper, or wider biopsy remain the most useful strategies to clinch the correct diagnosis. This review aims to present the key differential diagnoses of SCC, to discuss common diagnostic pitfalls, and to recommend ways to deal with diagnostically challenging cases.

Figure 1

Inverted follicular keratosis: lesion shows proliferative downgrowths of mature squamous epithelium with infundibular keratinization (H&E ×40).

Figure 2

Inverted follicular keratosis: higher magnification showing squamous eddies (H&E ×200).

Figure 3

Bowen disease: Shave biopsy specimen showing mainly papillomatous epidermal lesion with hyperkeratotic horn. Inset: closer view of the underlying lesional epidermis shows cells with nuclear pleomorphism, prominent nucleoli, and frequent and abnormal mitotic figures. (H&E, ×20; Inset: ×400).

Figure 4

Pseudoepitheliomatous hyperplasia featuring acanthotic squamous epithelium showing irregular thick finger-like downgrowths into the underlying dermis. (H&E, ×20).

Figure 5

Pseudoepitheliomatous hyperplasia: higher magnification view showing reactive-appearing squamous downgrowths with no significant cytologic atypia. The dermis shows mild chronic inflammation and granulation tissue formation (H&E, ×200).

Figure 6

Infundibulocystic hyperplasia: skin lesion showing follicular proliferative process with bland squamous cells and formation of dilated canals containing keratotic material. (H&E, ×40).

Figure 7

Infundibulocystic SCC: superficial areas showing infundibulocystic canals with deeper infiltrative squamous cell clusters featuring cellular atypia and mitoses (arrow). (H&E, ×100).

Figure 8

Verrucous hyperplasia: low power magnification view showing epidermal squamous proliferation with broad and superficial downgrowths of the epidermis. Overlying hyper-and parakeratosis is present. There is no atypia or koilocytes. (H&E, ×100).

Figure 9

Eccrine squamous syringometaplasia: bland appearing squamous islands in the dermis centered around eccrine lumina. Scattered lymphocytes are present in the surrounding dermis. (H&E, ×200).

Figure 10

Desmoplastic trichoepithelioma: macroscopic picture showing an ulcerative nodular lesion with raised rolled edges features which mimic SCC or BCC.

Figure 11

Desmoplastic trichoepithelioma: low power magnification showing hyperplastic downgrowths of epidermis with cords of basaloid tumor cells arranged in a pseudoinfiltrative pattern. (H&E, ×40).

Figure 12

Meningioma: medium power magnification showing syncytial sheets and whorls of tumor cells with bland nuclear features. The presence of nuclear pseudoinclusions, psammoma bodies and the absence of atypia allow the distinction from SCC. (H&E, ×200).

Figure 13

Endometriosis with decidualization: medium power magnification showing cystic space surrounded by large polygonal cells with basophilic cytoplasm and bland nuclei. The cyst wall is rimmed by a layer of endometrial cells (arrow). (H&E, ×200).

Figure 14

Keratoacanthoma: clinical photograph showing a well-circumscribed reddish nodule with erosion on the surface.

Figure 15

Keratoacanthoma: low power magnification showing a crateriform lesion which is filled with central keratinous plug and bounded by proliferative lesional squamous epithelium. (H&E, ×20).

Figure 16

Keratoacanthoma-like SCC: low power magnification showing a crateriform lesion with infiltrative islands and clusters of squamous cells at the base (arrow). (H&E, ×20).

Figure 17

Proliferating tricholemmal tumor: macroscopic photograph showing a circumscribed cutaneous reddish-pink nodular tumor with surface erosions.

Figure 18

Proliferating tricholemmal tumor: the lesion shows proliferation of squamous cells with clear cytoplasm and abrupt pilar-type keratinization (arrow) (H&E, ×200).

Figure 19

Clinical photograph showing a red, scaly plaque on the skin surface. The patient just had a biopsy performed with sutures still in place.

Figure 20

Bowen disease: medium-power magnification showing skin with full thickness epidermal dysplasia which is characterized by loss of the nuclear polarity, nuclear pleomorphism, and mitoses at all levels. The undulating deep epidermal contour and presence of eccrine ducts that have been colonized by the tumor cells (arrow) can potentially mimic invasion. (H&E, ×200).

Figure 21

Basal cell carcinoma: (a) low power magnification showing infiltrative irregular islands of basaloid tumor cells which appear to have more ample eosinophilic cytoplasm mimicking the appearance of SCC (H&E, ×100). (b) Tumor cells are diffusely positive for Ber-EP4. (c) Tumor cells also show diffuse positivity for bcl-2.

Figure 22

Keratotic BCC: medium-power magnification showing solid growth of tumor cells with foci of squamous differentiation featuring keratin pearls (arrow). Focal tumour-stromal cleft formation with myxoid substance is seen on the right. (H&E, ×200).

Figure 23

Spindle cell melanoma: medium-power magnification showing dermal pleomorphic spindle cell proliferation and focal junctional melanocytic nest (arrow). (H&E, ×100).

Figure 24

Metastatic SCC: low-power magnification showing solid growth of SCC which is predominantly located in the dermis and subcutaneous tissue. The overlying epidermis appears normal. This should raise suspicion of a metastatic deposit. (H&E, ×40).

Figure 25

Cutaneous anaplastic large cell lymphoma: low-power magnification showing hyperplastic squamous islands (arrow) associated proliferation of large neoplastic lymphocytes. (H&E, ×100).