Importance of Histopathology in Cutaneous Radiotherapy

Histology is important in cutaneous radiation to ensure the diagnosis is correct since different neoplasms are treated using different protocols. It is also important to ensure the lesion is encompassed in the field of therapy and that the energy and penetration is appropriate for the neoplasm at hand. For instance, superficial lesions may be treated differently than deep lesions.

The goals of cutaneous radiation therapy are to ensure the treatment will eradicate the cancer while delivering a therapeutic dose with minimal side effects. It is also very important that cutaneous radiation therapy not induce neoplasia.

This article focuses on several examples of challenges in diagnosis including metatypical basal cell carcinoma, combined squamous cell carcinoma and basal cell carcinoma, squamous cell carcinoma in situ, primary cutaneous carcinosarcoma, trichilemmal verruca, and inverted follicular keratosis. Additionally, the benefits and challenges of stereotactic radiation therapy (SRT) are touched upon.

Metatypical basal cell carcinoma is a variant of a basal cell carcinoma (BCC) that is an intermediate between nodular cystic BCC and squamous cell carcinoma (SCC). Histologically speaking, the cells are enlarged and are pleomorphic while lacking peripheral palisading. Abundant basophilic cytoplasm is present, but there is often no retraction artifact and a fibrous stoma may not be present. Metatypical BCC may simulate Merkel cell carcinoma, and even though it looks dangerous, it behaves like BCC. In terms of treatment, metatypical BCC is amenable to stereotactic radiation therapy.

Stereotactic radiation therapy—an advanced and modernized form of radiation therapy—allows high doses of radiation to be delivered to a small, focused area. It differs from conventional radiation in that it is able to exclude the surrounding normal tissues. SRT uses high-energy x-ray beams to shrink or control the growth of abnormal cells by either killing the cells directly or by disrupting the ability of the cells to grow.

In combined squamous cell carcinoma and basal cell carcinoma, an initial biopsy will show SCC or BCC, but upon subsequent evaluation of the excision specimen, there is evidence of both BCC and SCC. There are three possible reasons for this:

1. Collision tumor of coincidental BCC and SCC

2. Altered differentiation of BCC on recurrence may assume more aggressive histologic characteristics with squamous appearance

3. True basosquamous differentiation

It is important to recognize these reasons and ensure the biopsy is representative to avoid under-treatment.

Squamous cell carcinoma in situ is generally easily diagnosable even though there may be several variants clinically and histologically. One variant is pagetoid Bowen’s disease, which may stimulate Paget’s disease and melanoma in situ. SCC in situ may be able to be treated with a superficially penetrating beam. The most important challenge in diagnosing SCC in situ is to define the border, which may be very indistinct.

Primary cutaneous carcinosarcoma is a rare, biphasic tumor of malignant epithelial and mesenchymal components. The epithelial aspect may be keratinocytic, resembling BCC or SCC or adnexal. The sarcomatous component may resemble atypical fibroxanthoma, osteosarcoma, chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, or fibrosarcoma. Keratinocytic carcinosarcoma has a better prognosis than adnexal types (70% versus 25% 5-year survival rate). Primary cutaneous carcinosarcoma is a more aggressive lesion than SCC that requires surgical excision and not SRT.

Trichilemmal verruca may stimulate BCC histologically while verruca with squamous eddies (inverted follicular keratosis) may simulate SCC histologically. Trichilemmal verruca presents as a pink to whitish scar-like plaque of the trunk, extremities, head, and neck area.  It is important not to over-diagnose, which could lead to over-treatment.

Inverted follicular keratosis (verruca with squamous eddies) may be confused with SCC because of whorls of keratinocytes in nests that may be asymmetrically distributed. There are usually few if any mitoses present with no atypia. Inverted follicular keratosis is clinically usually not suggestive of SCC. If it doesn’t fit clinically and diagnosis comes back malignant, be sure to obtain a second opinion.

SRT is an excellent treatment option for many different conditions, but it does come with challenges. For example, reimbursement pressures and “turf” wars create unfortunate circumstances for dermatologists who want to use SRT.  Some use SRT inappropriately due to inadequate training and supervision. To avoid confusion as to when to use SRT, we at Cockerell Dermatopathology place a note on the report stating that the neoplasm in question is one that could be treated with SRT appropriately.

An accurate and complete diagnosis is essential to SRT use. If you perform SRT, establish a relationship with a dermatopathology laboratory that understands SRT and will be involved in the treatment planning.

References

Cockerell C. (2015). The importance of histopathology in cutaneous radiotherapy. [PowerPoint Presentation]

Stony Brook Cancer Center (2015). SRS and SRT: Stereotactic RadioSurgery and RadioTherapy. Retrieved December 2, 2015, from https://cancer.stonybrookmedicine.edu/diagnosis-treatment/radiation-oncology/treatment-technology/srs.