Which histologic findings are characteristic of postradiation therapy pathology?

Updated: Dec 30, 2020
  • Author: Kenneth A Iczkowski, MD; Chief Editor: Liang Cheng, MD  more...
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Answer

Following irradiation, the benign prostate shows acinar atrophy, with acinar distortion and decreased number and size of acini. In the most extreme form, only single cells may remain. Cytoplasm is usually decreased. Some nuclei are pyknotic, while others may be enlarged and atypical, exceeding the atypia of cancer. Basal cell hyperplasia or squamous metaplasia may exist. (See the images below.)

Postradiation Therapy Pathology of Prostate Cancer Postradiation Therapy Pathology of Prostate Cancer. In the nonneoplastic, irradiated prostate, nuclear enlargement and smudged chromatin are the most notable changes.
Postradiation Therapy Pathology of Prostate Cancer Postradiation Therapy Pathology of Prostate Cancer. This nuclear enlargement may be extreme, but no prominent secretory cell nucleoli exist.

In either benign or malignant prostate tissue, stromal fibrosis may occur following radiation therapy. Vascular changes include myointimal proliferation, luminal narrowing, and foamy macrophages. The hyalinized and thickened vessels provide a clue that the patient previously received radiation therapy, even if the clinician has not specified this. (See the image below.)

Postradiation Therapy Pathology of Prostate Cancer Postradiation Therapy Pathology of Prostate Cancer. In cases in which the history of irradiation is not given or is uncertain, stromal and vascular changes can cue the pathologist to recognize radiation effect. The stroma becomes fibrotic, and the cellularity of normal vessel walls (normal: left) increases because of smooth muscle proliferation (right).

Histologic features of irradiated cancer and reactive prostate, however, can overlap, regardless of the form of radiotherapy. Thus, it is reasonable to label some cases as indeterminate or atypical suspicious acinar proliferation (ASAP), a designation applied to most of the 20% of nonnegative biopsies in one study. [3] Microscopic findings following prostate irradiation are demonstrated in the images below.

Postradiation Therapy Pathology of Prostate Cancer Postradiation Therapy Pathology of Prostate Cancer. The preservation of at least a focal basal cell layer is a key finding (upper left).
Postradiation Therapy Pathology of Prostate Cancer Postradiation Therapy Pathology of Prostate Cancer. In basal cells, normally a single-layer (left), nuclear enlargement can be found. The cells may become so hyperplastic that they form several layers and secretory cells are inconspicuous (right). Irregular, potato-shaped nuclei are pathognomonic for basal cells.
Postradiation Therapy Pathology of Prostate Cancer Postradiation Therapy Pathology of Prostate Cancer. Identification of irradiated cancer is a problematic area in pathology now that increased numbers of posttreatment biopsies are being performed. Early changes include cytomegaly, vacuoles, and nucleomegaly with persistent single and, occasionally, double nucleoli in each nucleus (left). Later changes include atrophy and, sometimes, cytoplasmic vacuolation, with the nucleoli now being inconspicuous.
Postradiation Therapy Pathology of Prostate Cancer Postradiation Therapy Pathology of Prostate Cancer. In this matched set of photomicrographs from the same patient, compared with pretreatment grade 3 cancer (left), the main posttreatment change is atrophy (right). Note, however, the maintenance of an infiltrative pattern, angulated acini, absence of basal cells, and inspissated luminal blue mucin characteristic of cancer. Depending on the duration of irradiation, one may see all atrophic cancer acini, unchanged acini, or a combination of atrophic and unchanged acini.
Postradiation Therapy Pathology of Prostate Cancer Postradiation Therapy Pathology of Prostate Cancer. Needle biopsy specimen with postirradiation grade 3 cancer (left), a focus of high-grade prostatic intraepithelial neoplasia (PIN; center), and grade 4 cancer (right).
Postradiation Therapy Pathology of Prostate Cancer Postradiation Therapy Pathology of Prostate Cancer. The residual neoplasm loses architectural differentiation while retaining the cytologic features of cancer. The acini are decreased in number and smaller in size, with a haphazard arrangement.
Postradiation Therapy Pathology of Prostate Cancer Postradiation Therapy Pathology of Prostate Cancer. In the grade 4 component of cancer, the acinar luminal structure breaks down; overgrading the apparent single cells as grade 5 is a temptation. The nucleoli have disappeared, indicating maximal effect. Some cases have increased Paneth cells (Siders, 1992).
Postradiation Therapy Pathology of Prostate Cancer Postradiation Therapy Pathology of Prostate Cancer. In this biopsy specimen, high-grade prostatic intraepithelial neoplasia (PIN) with radiation effect is a helpful feature that should prompt a search for cancer. However, the frequency of PIN in irradiated prostate cancer (based on salvage prostatectomy findings) is reduced to 60% of cases (Cheng, 1998). In contrast, 82% of nonirradiated, step-sectioned prostates show high-grade PIN (McNeal, 1986).

Postradiation membranous urethral stenosis may occur in men treated for prostate cancer. Histologic findings may include vascular loss, higher collagen density/organization and increased hyalinized fibrosis (scarring), fat entrapment, and spindle cell change. [4]


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